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2016
Chypre M, Seaman J, Cordeiro O G, Willen L, Knoop K A, Buchanan A, Sainson R C, Williams I R, Yagita H, Schneider P, Mueller C G
Characterization and application of two RANK-specific antibodies with different biological activities Article de journal
Dans: Immunol.Lett., vol. 171, no. 1879-0542 (Electronic), p. 5–14, 2016.
Résumé | Liens | BibTeX | Étiquettes: Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy
@article{chypre_characterization_2016,
title = {Characterization and application of two RANK-specific antibodies with different biological activities},
author = {M Chypre and J Seaman and O G Cordeiro and L Willen and K A Knoop and A Buchanan and R C Sainson and I R Williams and H Yagita and P Schneider and C G Mueller},
doi = {10.1016/j.imlet.2016.01.003},
year = {2016},
date = {2016-03-01},
journal = {Immunol.Lett.},
volume = {171},
number = {1879-0542 (Electronic)},
pages = {5--14},
abstract = {Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-kappaB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-kappaB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools},
keywords = {Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy},
pubstate = {published},
tppubtype = {article}
}
Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-kappaB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-kappaB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools
2015
Lézot Frédéric, Chesneau Julie, Navet Benjamin, Gobin Bérengère, Amiaud Jérome, Choi YongWon, Yagita Hideo, Castaneda Beatriz, Berdal Ariane, Mueller Christopher G, Rédini Françoise, Heymann Dominique
Skeletal consequences of RANKL-blocking antibody (IK22-5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid Article de journal
Dans: Bone, vol. 73, p. 51–59, 2015, ISSN: 1873-2763.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, Bone Density Conservation Agents, Bone Development, Bone resorption, Diphosphonates, Female, Imidazoles, Inbred C57BL, Mice, Newborn, Pregnancy, RANK ligand, RANKL, Side effect, Skeleton growth, Team-Mueller, Tooth Eruption, Zoledronic acid
@article{lezot_skeletal_2015,
title = {Skeletal consequences of RANKL-blocking antibody (IK22-5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid},
author = {Frédéric Lézot and Julie Chesneau and Benjamin Navet and Bérengère Gobin and Jérome Amiaud and YongWon Choi and Hideo Yagita and Beatriz Castaneda and Ariane Berdal and Christopher G Mueller and Françoise Rédini and Dominique Heymann},
doi = {10.1016/j.bone.2014.12.011},
issn = {1873-2763},
year = {2015},
date = {2015-01-01},
journal = {Bone},
volume = {73},
pages = {51--59},
abstract = {High doses of bone resorption inhibitors are currently under evaluation in pediatric oncology. Previous works have evidenced transient arrest in long bone and skull bone growth and tooth eruption blockage when mice were treated with zoledronic acid (ZOL). The question of potential similar effects with a RANKL-blocking antibody (IK22.5) was raised. Sensitivity disparities in these inhibitors between mouse strains and synergic effects of zoledronic acid and a RANKL-blocking antibody were subsidiary questions. In order to answer these questions, newborn C57BL/6J and CD1 mice were injected every two or three days (4 injections in total so 7 or 10 days of treatment length) with high doses of a RANKL-blocking antibody. The consequences on the tibia, craniofacial bones and teeth were analyzed by μCT and histology at the end of the treatment and one, two and three months later. The results obtained showed that RANKL-blocking antibody injections induced a transient arrest of tibia and skull bone growth and an irreversible blockage of tooth eruption in C57BL/6J mice. In CD1 mice, tooth eruption defects were also present but only at much higher doses. Similar mouse strain differences were obtained with zoledronic acid. Finally, a synergic effect of the two inhibitors was evidenced. In conclusion as previously observed for bisphosphonates (ZOL), a RANKL-blocking antibody induced a transient arrest in long bone and skull bone growth and a blockage of tooth eruption with however disparities between mouse strains with regard to this last effect. A synergic effect of both bone resorption inhibitors was also demonstrated.},
keywords = {Animals, Antibodies, Bone Density Conservation Agents, Bone Development, Bone resorption, Diphosphonates, Female, Imidazoles, Inbred C57BL, Mice, Newborn, Pregnancy, RANK ligand, RANKL, Side effect, Skeleton growth, Team-Mueller, Tooth Eruption, Zoledronic acid},
pubstate = {published},
tppubtype = {article}
}
High doses of bone resorption inhibitors are currently under evaluation in pediatric oncology. Previous works have evidenced transient arrest in long bone and skull bone growth and tooth eruption blockage when mice were treated with zoledronic acid (ZOL). The question of potential similar effects with a RANKL-blocking antibody (IK22.5) was raised. Sensitivity disparities in these inhibitors between mouse strains and synergic effects of zoledronic acid and a RANKL-blocking antibody were subsidiary questions. In order to answer these questions, newborn C57BL/6J and CD1 mice were injected every two or three days (4 injections in total so 7 or 10 days of treatment length) with high doses of a RANKL-blocking antibody. The consequences on the tibia, craniofacial bones and teeth were analyzed by μCT and histology at the end of the treatment and one, two and three months later. The results obtained showed that RANKL-blocking antibody injections induced a transient arrest of tibia and skull bone growth and an irreversible blockage of tooth eruption in C57BL/6J mice. In CD1 mice, tooth eruption defects were also present but only at much higher doses. Similar mouse strain differences were obtained with zoledronic acid. Finally, a synergic effect of the two inhibitors was evidenced. In conclusion as previously observed for bisphosphonates (ZOL), a RANKL-blocking antibody induced a transient arrest in long bone and skull bone growth and a blockage of tooth eruption with however disparities between mouse strains with regard to this last effect. A synergic effect of both bone resorption inhibitors was also demonstrated.
2014
Flacher Vincent, Tripp Christoph H, Mairhofer David G, Steinman Ralph M, Stoitzner Patrizia, Idoyaga Juliana, Romani Nikolaus
Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance Article de journal
Dans: EMBO molecular medicine, vol. 6, no. 9, p. 1191–1204, 2014, ISSN: 1757-4684.
Résumé | Liens | BibTeX | Étiquettes: agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines
@article{flacher_murine_2014,
title = {Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance},
author = {Vincent Flacher and Christoph H Tripp and David G Mairhofer and Ralph M Steinman and Patrizia Stoitzner and Juliana Idoyaga and Nikolaus Romani},
doi = {10.15252/emmm.201303283},
issn = {1757-4684},
year = {2014},
date = {2014-09-01},
journal = {EMBO molecular medicine},
volume = {6},
number = {9},
pages = {1191--1204},
abstract = {Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8(+) T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin(+) dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8(+) T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8(+) T cells. Langerin/OVA combined with imiquimod could not prime CD8(+) T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin(+) dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8(+) T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.},
keywords = {agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8(+) T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin(+) dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8(+) T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8(+) T cells. Langerin/OVA combined with imiquimod could not prime CD8(+) T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin(+) dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8(+) T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
2012
Flacher V, Tripp C H, Haid B, Kissenpfennig A, Malissen B, Stoitzner P, Idoyaga J, Romani N
Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses Article de journal
Dans: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), p. 2146–2155, 2012.
Résumé | BibTeX | Étiquettes: administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic
@article{flacher_skin_2012,
title = {Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses},
author = {V Flacher and C H Tripp and B Haid and A Kissenpfennig and B Malissen and P Stoitzner and J Idoyaga and N Romani},
year = {2012},
date = {2012-03-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {2146--2155},
abstract = {Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8alpha(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8alpha(+) DCs are sufficient to subsequent CD8(+) T cell responses},
keywords = {administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic},
pubstate = {published},
tppubtype = {article}
}
Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8alpha(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8alpha(+) DCs are sufficient to subsequent CD8(+) T cell responses
Romani N, Flacher V, Tripp C H, Sparber F, Ebner S, Stoitzner P
Targeting skin dendritic cells to improve intradermal vaccination Article de journal
Dans: Current Topics in Microbiology and Immunology, vol. 351, p. 113–138, 2012, ISSN: 0070-217X.
Résumé | Liens | BibTeX | Étiquettes: Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases
@article{romani_targeting_2012,
title = {Targeting skin dendritic cells to improve intradermal vaccination},
author = {N Romani and V Flacher and C H Tripp and F Sparber and S Ebner and P Stoitzner},
doi = {10.1007/82_2010_118},
issn = {0070-217X},
year = {2012},
date = {2012-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {351},
pages = {113--138},
abstract = {Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.},
keywords = {Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases},
pubstate = {published},
tppubtype = {article}
}
Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.
2011
Venturelli Enrica, Fabbro Chiara, Chaloin Olivier, Ménard-Moyon Cécilia, Smulski Cristian R, Ros Tatiana Da, Kostarelos Kostas, Prato Maurizio, Bianco Alberto
Antibody covalent immobilization on carbon nanotubes and assessment of antigen binding Article de journal
Dans: Small (Weinheim an Der Bergstrasse, Germany), vol. 7, no. 15, p. 2179–2187, 2011, ISSN: 1613-6829.
Résumé | Liens | BibTeX | Étiquettes: Antibodies, Antigens, carbon, I2CT, Immobilized, Mucin-1, nanotechnology, Nanotubes, Protein Binding, Team-Bianco, Thermogravimetry
@article{venturelli_antibody_2011,
title = {Antibody covalent immobilization on carbon nanotubes and assessment of antigen binding},
author = {Enrica Venturelli and Chiara Fabbro and Olivier Chaloin and Cécilia Ménard-Moyon and Cristian R Smulski and Tatiana Da Ros and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},
doi = {10.1002/smll.201100137},
issn = {1613-6829},
year = {2011},
date = {2011-08-01},
journal = {Small (Weinheim an Der Bergstrasse, Germany)},
volume = {7},
number = {15},
pages = {2179--2187},
abstract = {Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in the design and preparation of nanotube-based conjugates for targeting cancer cells. For this purpose, an anti-MUC1 antibody (Ab) is linked to both multi-walled (MWCNTs) and double-walled carbon nanotubes (DWCNTs) using different synthetic strategies. The presence of the Ab attached to the nanotubes is confirmed by gel electrophoresis and thermogravimetric analysis. Most importantly, molecular recognition of the antigen by surface plasmon resonance is able to determine similar Ab binding capacities for both Ab-DWCNTs and Ab-MWCNTs. These results are very relevant for the design of future receptor-targeting strategies using chemically functionalized carbon nanotubes.},
keywords = {Antibodies, Antigens, carbon, I2CT, Immobilized, Mucin-1, nanotechnology, Nanotubes, Protein Binding, Team-Bianco, Thermogravimetry},
pubstate = {published},
tppubtype = {article}
}
Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in the design and preparation of nanotube-based conjugates for targeting cancer cells. For this purpose, an anti-MUC1 antibody (Ab) is linked to both multi-walled (MWCNTs) and double-walled carbon nanotubes (DWCNTs) using different synthetic strategies. The presence of the Ab attached to the nanotubes is confirmed by gel electrophoresis and thermogravimetric analysis. Most importantly, molecular recognition of the antigen by surface plasmon resonance is able to determine similar Ab binding capacities for both Ab-DWCNTs and Ab-MWCNTs. These results are very relevant for the design of future receptor-targeting strategies using chemically functionalized carbon nanotubes.
Canard B, Vachon H, Fontaine T, Pin J J, Paul S, Genin C, Mueller C G
Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue Article de journal
Dans: Immunol.Lett., vol. 135, no. 1879-0542 (Electronic), p. 165–172, 2011.
Résumé | BibTeX | Étiquettes: Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus
@article{canard_generation_2011,
title = {Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue},
author = {B Canard and H Vachon and T Fontaine and J J Pin and S Paul and C Genin and C G Mueller},
year = {2011},
date = {2011-01-01},
journal = {Immunol.Lett.},
volume = {135},
number = {1879-0542 (Electronic)},
pages = {165--172},
abstract = {DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor},
keywords = {Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus},
pubstate = {published},
tppubtype = {article}
}
DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor
2010
Flacher Vincent, Tripp Christoph H, Stoitzner Patrizia, Haid Bernhard, Ebner Susanne, Frari Barbara Del, Koch Franz, Park Chae Gyu, Steinman Ralph M, Idoyaga Juliana, Romani Nikolaus
Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis Article de journal
Dans: The Journal of Investigative Dermatology, vol. 130, no. 3, p. 755–762, 2010, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines
@article{flacher_epidermal_2010,
title = {Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis},
author = {Vincent Flacher and Christoph H Tripp and Patrizia Stoitzner and Bernhard Haid and Susanne Ebner and Barbara Del Frari and Franz Koch and Chae Gyu Park and Ralph M Steinman and Juliana Idoyaga and Nikolaus Romani},
doi = {10.1038/jid.2009.343},
issn = {1523-1747},
year = {2010},
date = {2010-03-01},
journal = {The Journal of Investigative Dermatology},
volume = {130},
number = {3},
pages = {755--762},
abstract = {Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.},
keywords = {Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.
Ménard-Moyon Cécilia, Kostarelos Kostas, Prato Maurizio, Bianco Alberto
Functionalized carbon nanotubes for probing and modulating molecular functions Article de journal
Dans: Chemistry & Biology, vol. 17, no. 2, p. 107–115, 2010, ISSN: 1879-1301.
Résumé | Liens | BibTeX | Étiquettes: Antibodies, Antigens, Atomic Force, Biosensing Techniques, carbon, Drug Delivery Systems, enzymes, Glycoproteins, I2CT, Ion Channels, Microscopy, Nanotubes, RNA, Small Interfering, Team-Bianco
@article{menard-moyon_functionalized_2010,
title = {Functionalized carbon nanotubes for probing and modulating molecular functions},
author = {Cécilia Ménard-Moyon and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},
doi = {10.1016/j.chembiol.2010.01.009},
issn = {1879-1301},
year = {2010},
date = {2010-02-01},
journal = {Chemistry & Biology},
volume = {17},
number = {2},
pages = {107--115},
abstract = {Carbon nanotubes (CNTs) entered the domain of biological research a few years ago, creating a significant amount of interest due to their extraordinary physicochemical properties. The integration of CNT-based strategies with biology necessitates a multidisciplinary approach that requires competences in the diverse fields of chemistry, physics, and life sciences. In the biomedical domain CNTs are extensively explored as novel drug delivery systems for therapy and diagnosis. Additionally, CNTs can also be designed as new tools for modulation of molecular functions, by directly affecting various biological processes or by interaction with bioactive molecules. The aim of this review is to discuss how CNTs can be exploited as new probes for molecular functions. The different sections illustrate various applications of CNTs, including gene silencing, surface cell interactions via glycoproteins, biosensing, intracellular drug delivery using an atomic force microscopy tip-based nanoinjector, modulation of antibody/antigen interaction and enzyme activity, and blocking of ion channels.},
keywords = {Antibodies, Antigens, Atomic Force, Biosensing Techniques, carbon, Drug Delivery Systems, enzymes, Glycoproteins, I2CT, Ion Channels, Microscopy, Nanotubes, RNA, Small Interfering, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Carbon nanotubes (CNTs) entered the domain of biological research a few years ago, creating a significant amount of interest due to their extraordinary physicochemical properties. The integration of CNT-based strategies with biology necessitates a multidisciplinary approach that requires competences in the diverse fields of chemistry, physics, and life sciences. In the biomedical domain CNTs are extensively explored as novel drug delivery systems for therapy and diagnosis. Additionally, CNTs can also be designed as new tools for modulation of molecular functions, by directly affecting various biological processes or by interaction with bioactive molecules. The aim of this review is to discuss how CNTs can be exploited as new probes for molecular functions. The different sections illustrate various applications of CNTs, including gene silencing, surface cell interactions via glycoproteins, biosensing, intracellular drug delivery using an atomic force microscopy tip-based nanoinjector, modulation of antibody/antigen interaction and enzyme activity, and blocking of ion channels.
Parietti Véronique, Chifflot Hélène, Sibilia Jean, Muller Sylviane, Monneaux Fanny
Rituximab treatment overcomes reduction of regulatory iNKT cells in patients with rheumatoid arthritis Article de journal
Dans: Clinical Immunology (Orlando, Fla.), vol. 134, no. 3, p. 331–339, 2010, ISSN: 1521-7035.
Résumé | Liens | BibTeX | Étiquettes: Adult, Age Factors, Aged, Antibodies, Antirheumatic Agents, arthritis, Female, Flow Cytometry, Humans, I2CT, Longitudinal Studies, Male, Middle Aged, Monneaux, Monoclonal, Murine-Derived, Natural Killer T-Cells, Nonparametric, rheumatoid, Rituximab, Sex Factors, Statistics, Team-Dumortier, Young Adult
@article{parietti_rituximab_2010,
title = {Rituximab treatment overcomes reduction of regulatory iNKT cells in patients with rheumatoid arthritis},
author = {Véronique Parietti and Hélène Chifflot and Jean Sibilia and Sylviane Muller and Fanny Monneaux},
doi = {10.1016/j.clim.2009.11.007},
issn = {1521-7035},
year = {2010},
date = {2010-01-01},
journal = {Clinical Immunology (Orlando, Fla.)},
volume = {134},
number = {3},
pages = {331--339},
abstract = {Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (ptextless0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency.},
keywords = {Adult, Age Factors, Aged, Antibodies, Antirheumatic Agents, arthritis, Female, Flow Cytometry, Humans, I2CT, Longitudinal Studies, Male, Middle Aged, Monneaux, Monoclonal, Murine-Derived, Natural Killer T-Cells, Nonparametric, rheumatoid, Rituximab, Sex Factors, Statistics, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (ptextless0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency.
Romani Nikolaus, Thurnher Martin, Idoyaga Juliana, Steinman Ralph M, Flacher Vincent
Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy Article de journal
Dans: Immunology and Cell Biology, vol. 88, no. 4, p. 424–430, 2010, ISSN: 1440-1711.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, C-Type, CD, CD14, CD1a, CROSS-PRESENTATION, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, Immunity, Immunotherapy, INDUCTION, Intradermal, Langerhans Cells, Lectins, Lymphocytes, Mannose-Binding Lectins, mouse, Receptor, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines
@article{romani_targeting_2010,
title = {Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy},
author = {Nikolaus Romani and Martin Thurnher and Juliana Idoyaga and Ralph M Steinman and Vincent Flacher},
doi = {10.1038/icb.2010.39},
issn = {1440-1711},
year = {2010},
date = {2010-01-01},
journal = {Immunology and Cell Biology},
volume = {88},
number = {4},
pages = {424--430},
abstract = {Vaccinations in medicine are commonly administered through the skin. Therefore, the vaccine is immunologically processed by antigen-presenting cells of the skin. There is recent evidence that the clinically less often used intradermal route is effective; in cases even superior to the conventional subcutaneous or intramuscular route. Professional antigen-presenting cells of the skin comprise epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(-) and dermal langerin(+) dendritic cells (DCs). In human skin, langerin(-) dermal DCs can be further subdivided on the basis of their reciprocal CD1a and CD14 expression. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Langerhans cells in human skin seem to be specialized for induction of cytotoxic T lymphocytes. Likewise, mouse Langerhans cells are capable of cross-presentation and of protecting against experimental tumours. It is desirable to harness these properties for immunotherapy. A promising strategy to dramatically improve the outcome of vaccinations is 'antigen targeting'. Thereby, the vaccine is delivered directly and selectively to defined types of skin DCs. Targeting is achieved by means of coupling antigen to antibodies that recognize cell surface receptors on DCs. This approach is being widely explored. Little is known, however, about the events that take place in the skin and the DCs subsets involved therein. This topic will be discussed in this article.},
keywords = {Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, C-Type, CD, CD14, CD1a, CROSS-PRESENTATION, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, Immunity, Immunotherapy, INDUCTION, Intradermal, Langerhans Cells, Lectins, Lymphocytes, Mannose-Binding Lectins, mouse, Receptor, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
Vaccinations in medicine are commonly administered through the skin. Therefore, the vaccine is immunologically processed by antigen-presenting cells of the skin. There is recent evidence that the clinically less often used intradermal route is effective; in cases even superior to the conventional subcutaneous or intramuscular route. Professional antigen-presenting cells of the skin comprise epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(-) and dermal langerin(+) dendritic cells (DCs). In human skin, langerin(-) dermal DCs can be further subdivided on the basis of their reciprocal CD1a and CD14 expression. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Langerhans cells in human skin seem to be specialized for induction of cytotoxic T lymphocytes. Likewise, mouse Langerhans cells are capable of cross-presentation and of protecting against experimental tumours. It is desirable to harness these properties for immunotherapy. A promising strategy to dramatically improve the outcome of vaccinations is 'antigen targeting'. Thereby, the vaccine is delivered directly and selectively to defined types of skin DCs. Targeting is achieved by means of coupling antigen to antibodies that recognize cell surface receptors on DCs. This approach is being widely explored. Little is known, however, about the events that take place in the skin and the DCs subsets involved therein. This topic will be discussed in this article.
2009
Flacher Vincent, Sparber Florian, Tripp Christoph H, Romani Nikolaus, Stoitzner Patrizia
Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy Article de journal
Dans: Cancer immunology, immunotherapy: CII, vol. 58, no. 7, p. 1137–1147, 2009, ISSN: 1432-0851.
Résumé | Liens | BibTeX | Étiquettes: Active, Animals, Antibodies, antibody, Antigen, Antigens, BLOOD, C-Type, cancer, CD, CD4-Positive T-Lymphocytes, CD4+ T cells, CD8-Positive T-Lymphocytes, CD8+ T cells, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Growth, Human, Humans, immune response, IMMUNE-RESPONSES, Immunization, Immunology, Immunotherapy, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Major Histocompatibility Complex, Mannose-Binding Lectins, metabolism, methods, MHC class I, MHC class I molecules, Mice, Neoplasm, Neoplasms, OVALBUMIN, Patients, PROGENITORS, Protein, Proteins, RESPONSES, review, Skin, T CELLS, T-CELLS, Team-Mueller, therapy, tumor
@article{flacher_targeting_2009,
title = {Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy},
author = {Vincent Flacher and Florian Sparber and Christoph H Tripp and Nikolaus Romani and Patrizia Stoitzner},
doi = {10.1007/s00262-008-0563-9},
issn = {1432-0851},
year = {2009},
date = {2009-07-01},
journal = {Cancer immunology, immunotherapy: CII},
volume = {58},
number = {7},
pages = {1137--1147},
abstract = {Langerhans cells, a subset of skin dendritic cells in the epidermis, survey peripheral tissue for invading pathogens. In recent functional studies it was proven that Langerhans cells can present exogenous antigen not merely on major histocompatibility complexes (MHC)-class II molecules to CD4+ T cells, but also on MHC-class I molecules to CD8+ T cells. Immune responses against topically applied antigen could be measured in skin-draining lymph nodes. Skin barrier disruption or co-application of adjuvants was required for maximal induction of T cell responses. Cytotoxic T cells induced by topically applied antigen inhibited tumor growth in vivo, thus underlining the potential of Langerhans cells for immunotherapy. Here we review recent work and report novel observations relating to the potential use of Langerhans cells for immunotherapy. We investigated the potential of epicutaneous immunization strategies in which resident skin dendritic cells are loaded with tumor antigen in situ. This contrasts with current clinical approaches, where dendritic cells generated from progenitors in blood are loaded with tumor antigen ex vivo before injection into cancer patients. In the current study, we applied either fluorescently labeled protein antigen or targeting antibodies against DEC-205/CD205 and langerin/CD207 topically onto barrier-disrupted skin and examined antigen capture and transport by Langerhans cells. Protein antigen could be detected in Langerhans cells in situ, and they were the main skin dendritic cell subset transporting antigen during emigration from skin explants. Potent in vivo proliferative responses of CD4+ and CD8+ T cells were measured after epicutaneous immunization with low amounts of protein antigen. Targeting antibodies were mainly transported by langerin+ migratory dendritic cells of which the majority represented migratory Langerhans cells and a smaller subset the new langerin+ dermal dendritic cell population located in the upper dermis. The preferential capture of topically applied antigen by Langerhans cells and their ability to induce potent CD4+ and CD8+ T cell responses emphasizes their potential for epicutaneous immunization strategies.},
keywords = {Active, Animals, Antibodies, antibody, Antigen, Antigens, BLOOD, C-Type, cancer, CD, CD4-Positive T-Lymphocytes, CD4+ T cells, CD8-Positive T-Lymphocytes, CD8+ T cells, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Growth, Human, Humans, immune response, IMMUNE-RESPONSES, Immunization, Immunology, Immunotherapy, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Major Histocompatibility Complex, Mannose-Binding Lectins, metabolism, methods, MHC class I, MHC class I molecules, Mice, Neoplasm, Neoplasms, OVALBUMIN, Patients, PROGENITORS, Protein, Proteins, RESPONSES, review, Skin, T CELLS, T-CELLS, Team-Mueller, therapy, tumor},
pubstate = {published},
tppubtype = {article}
}
Langerhans cells, a subset of skin dendritic cells in the epidermis, survey peripheral tissue for invading pathogens. In recent functional studies it was proven that Langerhans cells can present exogenous antigen not merely on major histocompatibility complexes (MHC)-class II molecules to CD4+ T cells, but also on MHC-class I molecules to CD8+ T cells. Immune responses against topically applied antigen could be measured in skin-draining lymph nodes. Skin barrier disruption or co-application of adjuvants was required for maximal induction of T cell responses. Cytotoxic T cells induced by topically applied antigen inhibited tumor growth in vivo, thus underlining the potential of Langerhans cells for immunotherapy. Here we review recent work and report novel observations relating to the potential use of Langerhans cells for immunotherapy. We investigated the potential of epicutaneous immunization strategies in which resident skin dendritic cells are loaded with tumor antigen in situ. This contrasts with current clinical approaches, where dendritic cells generated from progenitors in blood are loaded with tumor antigen ex vivo before injection into cancer patients. In the current study, we applied either fluorescently labeled protein antigen or targeting antibodies against DEC-205/CD205 and langerin/CD207 topically onto barrier-disrupted skin and examined antigen capture and transport by Langerhans cells. Protein antigen could be detected in Langerhans cells in situ, and they were the main skin dendritic cell subset transporting antigen during emigration from skin explants. Potent in vivo proliferative responses of CD4+ and CD8+ T cells were measured after epicutaneous immunization with low amounts of protein antigen. Targeting antibodies were mainly transported by langerin+ migratory dendritic cells of which the majority represented migratory Langerhans cells and a smaller subset the new langerin+ dermal dendritic cell population located in the upper dermis. The preferential capture of topically applied antigen by Langerhans cells and their ability to induce potent CD4+ and CD8+ T cell responses emphasizes their potential for epicutaneous immunization strategies.
2008
Muller Sylviane, Monneaux Fanny, Schall Nicolas, Rashkov Rasho K, Oparanov Boycho A, Wiesel Philippe, Geiger Jean-Marie, Zimmer Robert
Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial Article de journal
Dans: Arthritis and Rheumatism, vol. 58, no. 12, p. 3873–3883, 2008, ISSN: 0004-3591.
Résumé | Liens | BibTeX | Étiquettes: Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult
@article{muller_spliceosomal_2008,
title = {Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial},
author = {Sylviane Muller and Fanny Monneaux and Nicolas Schall and Rasho K Rashkov and Boycho A Oparanov and Philippe Wiesel and Jean-Marie Geiger and Robert Zimmer},
doi = {10.1002/art.24027},
issn = {0004-3591},
year = {2008},
date = {2008-01-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {12},
pages = {3873--3883},
abstract = {OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.},
keywords = {Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
Tripp Christoph H, Haid Bernhard, Flacher Vincent, Sixt Michael, Peter Hannes, Farkas Julia, Gschwentner Robert, Sorokin Lydia, Romani Nikolaus, Stoitzner Patrizia
The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1 Article de journal
Dans: Immunobiology, vol. 213, no. 9-10, p. 715–728, 2008, ISSN: 0171-2985.
Résumé | Liens | BibTeX | Étiquettes: anatomy & histology, Animals, Antibodies, antibody, BLOOD, Blood Vessels, CD31, Cell Movement, Culture, cytology, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, DERMIS, EAR, electron microscopy, ENDOTHELIUM, Expression, GLYCOPROTEIN, Glycoproteins, hyaluronan, imiquimod, Immunology, Immunotherapy, In vivo, Inbred BALB C, Inbred C57BL, Langerhans Cells, ligand, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, LYVE-1, Membrane Transport Proteins, metabolism, MHC, Mice, migration, mouse, murine, physiology, priming, Protein, Receptor, Skin, tape stripping, Team-Mueller, tolerance
@article{tripp_lymph_2008,
title = {The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1},
author = {Christoph H Tripp and Bernhard Haid and Vincent Flacher and Michael Sixt and Hannes Peter and Julia Farkas and Robert Gschwentner and Lydia Sorokin and Nikolaus Romani and Patrizia Stoitzner},
doi = {10.1016/j.imbio.2008.07.025},
issn = {0171-2985},
year = {2008},
date = {2008-01-01},
journal = {Immunobiology},
volume = {213},
number = {9-10},
pages = {715--728},
abstract = {Langerhans cells and dermal dendritic cells migrate to the draining lymph nodes through dermal lymphatic vessels. They do so in the steady-state and under inflammatory conditions. Peripheral T cell tolerance or T cell priming, respectively, are the consequences of migration. The nature of dendritic cell-containing vessels was mostly defined by electron microscopy or by their lack of blood endothelial markers. Selective markers for murine lymph endothelium were hitherto rare or not available. Here, we utilised recently developed antibodies against the murine hyaluronan receptor, LYVE-1, to study the lymph vessel network in mouse skin in more detail. In hairless skin from the ears, lymph vessels were spread out in a horizontal plane. They formed anastomoses, and they possessed frequent blind endings that were occasionally open. Lymph vessels were wider than blood vessels, which were identified by their strong CD31 expression. In body wall skin LYVE-1 reactive vessels did not extend laterally but they dived straight down into the deeper dermis. There, they are connected to each other and formed a network similar to ear skin. The number and width of lymph vessels did not grossly change upon inflammatory stimuli such as skin explant culture or tape stripping. There were also no marked changes in caliber in response to the TLR 7/8 ligand Imiquimod. Double-labelling experiments of cultured skin showed that most of the strongly cell surface MHC II-expressing (i.e. activated) dendritic cells were confined to the lymph vessels. Langerin/CD207(+) cells within this population appeared later than dermal dendritic cells, i.e. langerin-negative cells. Comparable results were obtained after stimulating the skin in vivo with the TLR 7/8 ligand Imiquimod or by tape stripping. In untreated skin (i.e. steady state) a few MHC II(+) and Langerin/CD207(+) cells, presumably migrating skin dendritic cells including epidermal Langerhans cells, were consistently observed within the lymph vessels. The novel antibody reagents may serve as important tools to further study the dendritic cell traffic in the skin under physiological conditions as well as in conditions of adoptive dendritic cell transfer in immunotherapy.},
keywords = {anatomy & histology, Animals, Antibodies, antibody, BLOOD, Blood Vessels, CD31, Cell Movement, Culture, cytology, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, DERMIS, EAR, electron microscopy, ENDOTHELIUM, Expression, GLYCOPROTEIN, Glycoproteins, hyaluronan, imiquimod, Immunology, Immunotherapy, In vivo, Inbred BALB C, Inbred C57BL, Langerhans Cells, ligand, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, LYVE-1, Membrane Transport Proteins, metabolism, MHC, Mice, migration, mouse, murine, physiology, priming, Protein, Receptor, Skin, tape stripping, Team-Mueller, tolerance},
pubstate = {published},
tppubtype = {article}
}
Langerhans cells and dermal dendritic cells migrate to the draining lymph nodes through dermal lymphatic vessels. They do so in the steady-state and under inflammatory conditions. Peripheral T cell tolerance or T cell priming, respectively, are the consequences of migration. The nature of dendritic cell-containing vessels was mostly defined by electron microscopy or by their lack of blood endothelial markers. Selective markers for murine lymph endothelium were hitherto rare or not available. Here, we utilised recently developed antibodies against the murine hyaluronan receptor, LYVE-1, to study the lymph vessel network in mouse skin in more detail. In hairless skin from the ears, lymph vessels were spread out in a horizontal plane. They formed anastomoses, and they possessed frequent blind endings that were occasionally open. Lymph vessels were wider than blood vessels, which were identified by their strong CD31 expression. In body wall skin LYVE-1 reactive vessels did not extend laterally but they dived straight down into the deeper dermis. There, they are connected to each other and formed a network similar to ear skin. The number and width of lymph vessels did not grossly change upon inflammatory stimuli such as skin explant culture or tape stripping. There were also no marked changes in caliber in response to the TLR 7/8 ligand Imiquimod. Double-labelling experiments of cultured skin showed that most of the strongly cell surface MHC II-expressing (i.e. activated) dendritic cells were confined to the lymph vessels. Langerin/CD207(+) cells within this population appeared later than dermal dendritic cells, i.e. langerin-negative cells. Comparable results were obtained after stimulating the skin in vivo with the TLR 7/8 ligand Imiquimod or by tape stripping. In untreated skin (i.e. steady state) a few MHC II(+) and Langerin/CD207(+) cells, presumably migrating skin dendritic cells including epidermal Langerhans cells, were consistently observed within the lymph vessels. The novel antibody reagents may serve as important tools to further study the dendritic cell traffic in the skin under physiological conditions as well as in conditions of adoptive dendritic cell transfer in immunotherapy.
2007
Monneaux F, Muller S
[The spliceosome and its interest for lupus therapy] Article de journal
Dans: La Revue De Medecine Interne, vol. 28, no. 10, p. 725–728, 2007, ISSN: 0248-8663.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Motifs, Animals, Antibodies, CD4-Positive T-Lymphocytes, Conserved Sequence, DNA, Epitopes, Haplotypes, Humans, I2CT, Immune Tolerance, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Phosphoserine, Protein, Recombinant, Ribonucleoprotein, Sequence Analysis, Serine, Spliceosomes, Systemic, Team-Dumortier, U1 Small Nuclear
@article{monneaux_spliceosome_2007,
title = {[The spliceosome and its interest for lupus therapy]},
author = {F Monneaux and S Muller},
doi = {10.1016/j.revmed.2007.05.003},
issn = {0248-8663},
year = {2007},
date = {2007-01-01},
journal = {La Revue De Medecine Interne},
volume = {28},
number = {10},
pages = {725--728},
abstract = {INTRODUCTION: The spliceosome, which is a particle containing a molecule of U-RNA and proteins that are specific to each U ribonuclear particle (U-snRNP) or common to every U-snRNPs, is one of the numerous nuclear targets recognized by the antibodies (Abs) and CD4+ T cells from patients with systemic lupus erythematosus and lupus mice.
EXEGESIS: We recently characterized a peptide from the spliceosomal protein U1-70K (sequence 131-151), which is recognized by the Abs and CD4+ T cells from lupus mice and patients. This peptide contains a conserved RNP1 motif, which is also present in other spliceosomal proteins targeted by the Abs from individuals with lupus. We further showed that peptide 131-151 containing a phosphoserine at position 140 (peptide P140) possessed tolerogenic properties in lupus mice and was recognized by the Abs and CD4+ T cells from lupus patients.
CONCLUSION: Thanks to its RNP1 motif, the peptide P140 might play an important role in the initiation and perpetuation steps of the humoral and cellular immune response diversification in lupus individuals. Therapeutic and particularly immunomodulating properties of P140 peptide are being evaluated in humans (a phase III clinical trial will be undertaken in the next weeks).},
keywords = {Amino Acid Motifs, Animals, Antibodies, CD4-Positive T-Lymphocytes, Conserved Sequence, DNA, Epitopes, Haplotypes, Humans, I2CT, Immune Tolerance, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Phosphoserine, Protein, Recombinant, Ribonucleoprotein, Sequence Analysis, Serine, Spliceosomes, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: The spliceosome, which is a particle containing a molecule of U-RNA and proteins that are specific to each U ribonuclear particle (U-snRNP) or common to every U-snRNPs, is one of the numerous nuclear targets recognized by the antibodies (Abs) and CD4+ T cells from patients with systemic lupus erythematosus and lupus mice.
EXEGESIS: We recently characterized a peptide from the spliceosomal protein U1-70K (sequence 131-151), which is recognized by the Abs and CD4+ T cells from lupus mice and patients. This peptide contains a conserved RNP1 motif, which is also present in other spliceosomal proteins targeted by the Abs from individuals with lupus. We further showed that peptide 131-151 containing a phosphoserine at position 140 (peptide P140) possessed tolerogenic properties in lupus mice and was recognized by the Abs and CD4+ T cells from lupus patients.
CONCLUSION: Thanks to its RNP1 motif, the peptide P140 might play an important role in the initiation and perpetuation steps of the humoral and cellular immune response diversification in lupus individuals. Therapeutic and particularly immunomodulating properties of P140 peptide are being evaluated in humans (a phase III clinical trial will be undertaken in the next weeks).
EXEGESIS: We recently characterized a peptide from the spliceosomal protein U1-70K (sequence 131-151), which is recognized by the Abs and CD4+ T cells from lupus mice and patients. This peptide contains a conserved RNP1 motif, which is also present in other spliceosomal proteins targeted by the Abs from individuals with lupus. We further showed that peptide 131-151 containing a phosphoserine at position 140 (peptide P140) possessed tolerogenic properties in lupus mice and was recognized by the Abs and CD4+ T cells from lupus patients.
CONCLUSION: Thanks to its RNP1 motif, the peptide P140 might play an important role in the initiation and perpetuation steps of the humoral and cellular immune response diversification in lupus individuals. Therapeutic and particularly immunomodulating properties of P140 peptide are being evaluated in humans (a phase III clinical trial will be undertaken in the next weeks).
2004
van Mierlo Geertje J D, Boonman Zita F H M, Dumortier Hélène M H, den Boer Annemieke Th, Fransen Marieke F, Nouta Jan, van der Voort Ellen I H, Offringa Rienk, Toes René E M, Melief Cornelis J M
Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 173, no. 11, p. 6753–6759, 2004, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral
@article{van_mierlo_activation_2004,
title = {Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication},
author = {Geertje J D van Mierlo and Zita F H M Boonman and Hélène M H Dumortier and Annemieke Th den Boer and Marieke F Fransen and Jan Nouta and Ellen I H van der Voort and Rienk Offringa and René E M Toes and Cornelis J M Melief},
doi = {10.4049/jimmunol.173.11.6753},
issn = {0022-1767},
year = {2004},
date = {2004-12-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {173},
number = {11},
pages = {6753--6759},
abstract = {The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.},
keywords = {Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral},
pubstate = {published},
tppubtype = {article}
}
The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.
Monneaux Fanny, Muller Sylviane
Peptide-based immunotherapy of systemic lupus erythematosus Article de journal
Dans: Autoimmunity Reviews, vol. 3, no. 1, p. 16–24, 2004, ISSN: 1568-9972.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, Antinuclear, Epitopes, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Mice, Monneaux, Peptides, Systemic, T-Lymphocytes, Team-Dumortier
@article{monneaux_peptide-based_2004,
title = {Peptide-based immunotherapy of systemic lupus erythematosus},
author = {Fanny Monneaux and Sylviane Muller},
doi = {10.1016/S1568-9972(03)00061-2},
issn = {1568-9972},
year = {2004},
date = {2004-01-01},
journal = {Autoimmunity Reviews},
volume = {3},
number = {1},
pages = {16--24},
abstract = {Current drug-based therapy for systemic lupus erythematosus (SLE) are non-specific and often counterbalanced by adverse effects. Current research aims at developing specific treatments that target deleterious cells only and not the whole immune system. This strategy requires the identification of sequences derived from major lupus autoantigens, responsible for the activation of autoreactive B and T cells. This review summarizes the identification and characterization of peptides, which are able to modulate T cells ex vivo, and describes the promising results obtained after administration of some of these peptides in lupus mice. Although these therapeutic trials are encouraging, the precise mode of action of peptide-based immunotherapy is still elusive. Here, we discuss the possible mechanisms leading to T-cell tolerance induction and the feasibility of extending the success of peptide-based therapy from animal models to human.},
keywords = {Animals, Antibodies, Antinuclear, Epitopes, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Mice, Monneaux, Peptides, Systemic, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Current drug-based therapy for systemic lupus erythematosus (SLE) are non-specific and often counterbalanced by adverse effects. Current research aims at developing specific treatments that target deleterious cells only and not the whole immune system. This strategy requires the identification of sequences derived from major lupus autoantigens, responsible for the activation of autoreactive B and T cells. This review summarizes the identification and characterization of peptides, which are able to modulate T cells ex vivo, and describes the promising results obtained after administration of some of these peptides in lupus mice. Although these therapeutic trials are encouraging, the precise mode of action of peptide-based immunotherapy is still elusive. Here, we discuss the possible mechanisms leading to T-cell tolerance induction and the feasibility of extending the success of peptide-based therapy from animal models to human.
2003
Pantarotto Davide, Partidos Charalambos D, Hoebeke Johan, Brown Fred, Kramer Ed, Briand Jean-Paul, Muller Sylviane, Prato Maurizio, Bianco Alberto
Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses Article de journal
Dans: Chemistry & Biology, vol. 10, no. 10, p. 961–966, 2003, ISSN: 1074-5521.
Liens | BibTeX | Étiquettes: Animals, Antibodies, Antigen-Antibody Reactions, carbon, Drug Delivery Systems, Epitopes, Foot-and-Mouth Disease Virus, I2CT, Immunization, Mice, Monoclonal, Nanotubes, Neutralization Tests, Peptides, Team-Bianco, Vaccines, Viral
@article{pantarotto_immunization_2003,
title = {Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses},
author = {Davide Pantarotto and Charalambos D Partidos and Johan Hoebeke and Fred Brown and Ed Kramer and Jean-Paul Briand and Sylviane Muller and Maurizio Prato and Alberto Bianco},
doi = {10.1016/j.chembiol.2003.09.011},
issn = {1074-5521},
year = {2003},
date = {2003-10-01},
journal = {Chemistry & Biology},
volume = {10},
number = {10},
pages = {961--966},
keywords = {Animals, Antibodies, Antigen-Antibody Reactions, carbon, Drug Delivery Systems, Epitopes, Foot-and-Mouth Disease Virus, I2CT, Immunization, Mice, Monoclonal, Nanotubes, Neutralization Tests, Peptides, Team-Bianco, Vaccines, Viral},
pubstate = {published},
tppubtype = {article}
}
2002
Munier Anne-Isabelle, Doucet Daniel, Perrodou Emmanuel, Zachary Daniel, Meister Marie, Hoffmann Jules A, Janeway Charles A, Lagueux Marie
PVF2, a PDGF/VEGF-like growth factor, induces hemocyte proliferation in Drosophila larvae Article de journal
Dans: EMBO Rep., vol. 3, no. 12, p. 1195–1200, 2002, ISSN: 1469-221X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, Blotting, Cell Differentiation, Hemocytes, hoffmann, Immunohistochemistry, Larva, ligands, M3i, Platelet-Derived Growth Factor, Receptors, Vascular Endothelial Growth Factor, Western
@article{munier_pvf2_2002,
title = {PVF2, a PDGF/VEGF-like growth factor, induces hemocyte proliferation in Drosophila larvae},
author = {Anne-Isabelle Munier and Daniel Doucet and Emmanuel Perrodou and Daniel Zachary and Marie Meister and Jules A Hoffmann and Charles A Janeway and Marie Lagueux},
doi = {10.1093/embo-reports/kvf242},
issn = {1469-221X},
year = {2002},
date = {2002-12-01},
journal = {EMBO Rep.},
volume = {3},
number = {12},
pages = {1195--1200},
abstract = {Blood cells play a crucial role in both morphogenetic and immunological processes in Drosophila, yet the factors regulating their proliferation remain largely unknown. In order to address this question, we raised antibodies against a tumorous blood cell line and identified an antigenic determinant that marks the surface of prohemocytes and also circulating plasmatocytes in larvae. This antigen was identified as a Drosophila homolog of the mammalian receptor for platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF). The Drosophila receptor controls cell proliferation in vitro. By overexpressing in vivo one of its putative ligands, PVF2, we induced a dramatic increase in circulating hemocytes. These results identify the PDGF/VEGF receptor homolog and one of its ligands as important players in Drosophila hematopoiesis.},
keywords = {Animals, Antibodies, Blotting, Cell Differentiation, Hemocytes, hoffmann, Immunohistochemistry, Larva, ligands, M3i, Platelet-Derived Growth Factor, Receptors, Vascular Endothelial Growth Factor, Western},
pubstate = {published},
tppubtype = {article}
}
Blood cells play a crucial role in both morphogenetic and immunological processes in Drosophila, yet the factors regulating their proliferation remain largely unknown. In order to address this question, we raised antibodies against a tumorous blood cell line and identified an antigenic determinant that marks the surface of prohemocytes and also circulating plasmatocytes in larvae. This antigen was identified as a Drosophila homolog of the mammalian receptor for platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF). The Drosophila receptor controls cell proliferation in vitro. By overexpressing in vivo one of its putative ligands, PVF2, we induced a dramatic increase in circulating hemocytes. These results identify the PDGF/VEGF receptor homolog and one of its ligands as important players in Drosophila hematopoiesis.
1999
Vlasov A V, Helm M, Naumov V A, Breusov A A, Buneva V N, Florentz C, Giege R, Nevinskii G A
[Features of tRNA hydrolysis by autoantibodies from blood serum of patients with certain autoimmune and virus diseases] Article de journal
Dans: Mol Biol (Mosk), vol. 33, no. 5, p. 866-872, 1999, ISBN: 10579192, (0026-8984 Journal Article).
Liens | BibTeX | Étiquettes: Antibodies, Autoimmune/blood/*immunology Virus Diseases/blood/*immunology, Catalytic/metabolism Autoantibodies/*blood Base Sequence Human Hydrolysis Lupus Erythematosus, FLORENTZ, Systemic/blood/*immunology Molecular Sequence Data Nucleic Acid Conformation RNA, Transfer/chemistry/*metabolism Thyroiditis, Unité ARN
@article{,
title = {[Features of tRNA hydrolysis by autoantibodies from blood serum of patients with certain autoimmune and virus diseases]},
author = {A V Vlasov and M Helm and V A Naumov and A A Breusov and V N Buneva and C Florentz and R Giege and G A Nevinskii},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10579192},
isbn = {10579192},
year = {1999},
date = {1999-01-01},
journal = {Mol Biol (Mosk)},
volume = {33},
number = {5},
pages = {866-872},
note = {0026-8984
Journal Article},
keywords = {Antibodies, Autoimmune/blood/*immunology Virus Diseases/blood/*immunology, Catalytic/metabolism Autoantibodies/*blood Base Sequence Human Hydrolysis Lupus Erythematosus, FLORENTZ, Systemic/blood/*immunology Molecular Sequence Data Nucleic Acid Conformation RNA, Transfer/chemistry/*metabolism Thyroiditis, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
1998
Hoet R M, Raats J M, de Wildt R, Dumortier H, Muller S, van den Hoogen F, van Venrooij W J
Dans: Molecular Immunology, vol. 35, no. 16, p. 1045–1055, 1998, ISSN: 0161-5890.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear
@article{hoet_human_1998,
title = {Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the U1snRNP associated U1C protein; epitope mapping, immunolocalization and V-gene usage},
author = {R M Hoet and J M Raats and R de Wildt and H Dumortier and S Muller and F van den Hoogen and W J van Venrooij},
doi = {10.1016/s0161-5890(98)00093-5},
issn = {0161-5890},
year = {1998},
date = {1998-11-01},
journal = {Molecular Immunology},
volume = {35},
number = {16},
pages = {1045--1055},
abstract = {To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.},
keywords = {Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.
1997
Mézière C, Viguier M, Dumortier H, Lo-Man R, Leclerc C, Guillet J G, Briand J P, Muller S
In vivo Ŧ helper cell response to retro-inverso peptidomimetics Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 159, no. 7, p. 3230–3237, 1997, ISSN: 0022-1767.
Résumé | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral
@article{meziere_vivo_1997,
title = {In vivo Ŧ helper cell response to retro-inverso peptidomimetics},
author = {C Mézière and M Viguier and H Dumortier and R Lo-Man and C Leclerc and J G Guillet and J P Briand and S Muller},
issn = {0022-1767},
year = {1997},
date = {1997-10-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {159},
number = {7},
pages = {3230--3237},
abstract = {Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.},
keywords = {Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral},
pubstate = {published},
tppubtype = {article}
}
Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.
Vlassov A V, Andrievskaya O A, Kanyshkova T G, Baranovsky A G, Naumov V A, Breusov A A, Giege R, Buneva V N, Nevinsky G A
RNA-hydrolyzing antibodies from peripheral blood of patients with lupus erythematosus Article de journal
Dans: Biochemistry (Mosc), vol. 62, no. 5, p. 474-479, 1997, ISBN: 9275287, (0006-2979 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Antibodies, Catalytic/*blood Human Hydrolysis Lupus Erythematosus, Lys/chemistry/*metabolism, Systemic/blood/*immunology Nucleic Acid Conformation RNA, Transfer, Unité ARN
@article{,
title = {RNA-hydrolyzing antibodies from peripheral blood of patients with lupus erythematosus},
author = {A V Vlassov and O A Andrievskaya and T G Kanyshkova and A G Baranovsky and V A Naumov and A A Breusov and R Giege and V N Buneva and G A Nevinsky},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9275287},
isbn = {9275287},
year = {1997},
date = {1997-01-01},
journal = {Biochemistry (Mosc)},
volume = {62},
number = {5},
pages = {474-479},
abstract = {Experiments and hydrolysis of substrates with known spatial structures (such as yeast tRNAPhe, as well as normal and mutant tRNALys from human mitochondria produced by transcription of the appropriate DNA species, that is, RNA genes) were performed to study the ribonuclease activity of antibodies isolated from blood sera of patients with systemic lupus erythematosus (SLE). The antibody preparations contained two types of ribonuclease activities: the first corresponded to the specificity of ribonuclease A and was found during hydrolysis at low salt concentrations, whereas the second was stimulated by Mg2+ and displayed unique specificity toward double-stranded regions of the substrate. The possible use of the antibody preparations as tools for structural studies of conformational differences between RNA molecules was examined. In experiments with unmodified and mutant tRNALys species differing in one base found in the T-loop, we found that hydrolysis with SLE antibodies can detect small local structural changes in RNA under physiological conditions.},
note = {0006-2979
Journal Article},
keywords = {Antibodies, Catalytic/*blood Human Hydrolysis Lupus Erythematosus, Lys/chemistry/*metabolism, Systemic/blood/*immunology Nucleic Acid Conformation RNA, Transfer, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Experiments and hydrolysis of substrates with known spatial structures (such as yeast tRNAPhe, as well as normal and mutant tRNALys from human mitochondria produced by transcription of the appropriate DNA species, that is, RNA genes) were performed to study the ribonuclease activity of antibodies isolated from blood sera of patients with systemic lupus erythematosus (SLE). The antibody preparations contained two types of ribonuclease activities: the first corresponded to the specificity of ribonuclease A and was found during hydrolysis at low salt concentrations, whereas the second was stimulated by Mg2+ and displayed unique specificity toward double-stranded regions of the substrate. The possible use of the antibody preparations as tools for structural studies of conformational differences between RNA molecules was examined. In experiments with unmodified and mutant tRNALys species differing in one base found in the T-loop, we found that hydrolysis with SLE antibodies can detect small local structural changes in RNA under physiological conditions.
Baranovsky A G, Matushin V G, Vlassov A V, Zabara V G, Naumov V A, Giege R, Buneva V N, Nevinsky G A
DNA- and RNA-hydrolyzing antibodies from the blood of patients with various forms of viral hepatitis Article de journal
Dans: Biochemistry (Mosc), vol. 62, no. 12, p. 1358-1366, 1997, ISBN: 9481869, (0006-2979 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Antibodies, Antinuclear/*blood/immunology Antibodies, Catalytic/*blood/isolation & purification Base Sequence Chromatography, Gel DNA/*metabolism Deoxyribonucleases/metabolism Electrophoresis, Human/blood/*immunology Human Hydrolysis Molecular Sequence Data Nucleic Acid Conformation RNA/chemistry/*metabolism Ribonucleases/metabolism Support, Non-U.S. Gov't, Polyacrylamide Gel Hepatitis, Unité ARN, Viral
@article{,
title = {DNA- and RNA-hydrolyzing antibodies from the blood of patients with various forms of viral hepatitis},
author = {A G Baranovsky and V G Matushin and A V Vlassov and V G Zabara and V A Naumov and R Giege and V N Buneva and G A Nevinsky},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9481869},
isbn = {9481869},
year = {1997},
date = {1997-01-01},
journal = {Biochemistry (Mosc)},
volume = {62},
number = {12},
pages = {1358-1366},
abstract = {Antibodies (Abs) hydrolyzing proteins, DNA, and RNA are detected in the blood of patients with various autoimmune diseases. In the present work, homogeneous preparations of IgG Abs from the blood of the healthy donors as well as patients with A, B, C, and delta types of viral hepatitis, influenza, pneumonia, tuberculosis, tonsillitis, duodenal ulcer, and some types of cancer were purified. For the first time, the fraction of IgG and its Fab fragments of patients with viral hepatitis were shown to have high DNA- and RNA-hydrolyzing activity. In case of Abs from the healthy donors and patients with other diseases, high activity of Abs was not detected. The data obtained by various methods indicate that the activity of hepatitis Abs is an intrinsic property of the immunoglobulins. The relative rates of hydrolysis of cCMP, poly(U), poly(A), poly(C), and tRNA(Phe) by hepatitis Abs were compared with those of RNase A and other RNases from human blood. Significant differences in activities of Abs and nucleases in hydrolysis of model substrates were demonstrated. Thus, catalytically active Abs can appear in the blood of patients not only with autoimmune disorders, but with viral diseases as well.},
note = {0006-2979
Journal Article},
keywords = {Antibodies, Antinuclear/*blood/immunology Antibodies, Catalytic/*blood/isolation & purification Base Sequence Chromatography, Gel DNA/*metabolism Deoxyribonucleases/metabolism Electrophoresis, Human/blood/*immunology Human Hydrolysis Molecular Sequence Data Nucleic Acid Conformation RNA/chemistry/*metabolism Ribonucleases/metabolism Support, Non-U.S. Gov't, Polyacrylamide Gel Hepatitis, Unité ARN, Viral},
pubstate = {published},
tppubtype = {article}
}
Antibodies (Abs) hydrolyzing proteins, DNA, and RNA are detected in the blood of patients with various autoimmune diseases. In the present work, homogeneous preparations of IgG Abs from the blood of the healthy donors as well as patients with A, B, C, and delta types of viral hepatitis, influenza, pneumonia, tuberculosis, tonsillitis, duodenal ulcer, and some types of cancer were purified. For the first time, the fraction of IgG and its Fab fragments of patients with viral hepatitis were shown to have high DNA- and RNA-hydrolyzing activity. In case of Abs from the healthy donors and patients with other diseases, high activity of Abs was not detected. The data obtained by various methods indicate that the activity of hepatitis Abs is an intrinsic property of the immunoglobulins. The relative rates of hydrolysis of cCMP, poly(U), poly(A), poly(C), and tRNA(Phe) by hepatitis Abs were compared with those of RNase A and other RNases from human blood. Significant differences in activities of Abs and nucleases in hydrolysis of model substrates were demonstrated. Thus, catalytically active Abs can appear in the blood of patients not only with autoimmune disorders, but with viral diseases as well.