Dieker J, Cisterna B, Monneaux F, Decossas M, van der Vlag J, Biggiogera M, Muller S
Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K Article de journal
Dans: Cell Death and Differentiation, vol. 15, no. 4, p. 793–804, 2008, ISSN: 1350-9047.
Résumé | Liens | BibTeX | Étiquettes: Apoptosis, Autoantigens, Autoimmunity, Caspase 3, Chromatin, HeLa Cells, Humans, I2CT, Jurkat Cells, Lupus Erythematosus, Monneaux, Phosphorylation, Post-Translational, Protein Phosphatase 1, Protein Processing, Protein Transport, Recombinant Proteins, Ribonucleoprotein, RNA Splicing, Serine, Spliceosomes, Systemic, Team-Dumortier, Time Factors, U1 Small Nuclear
@article{dieker_apoptosis-linked_2008,
title = {Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K},
author = {J Dieker and B Cisterna and F Monneaux and M Decossas and J van der Vlag and M Biggiogera and S Muller},
doi = {10.1038/sj.cdd.4402312},
issn = {1350-9047},
year = {2008},
date = {2008-01-01},
journal = {Cell Death and Differentiation},
volume = {15},
number = {4},
pages = {793--804},
abstract = {Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading to sequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essential components of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before the cleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within the RNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serine residues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneous ectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomal U1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery during early apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellular localization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigen during the autoimmune disease systemic lupus erythematosus.},
keywords = {Apoptosis, Autoantigens, Autoimmunity, Caspase 3, Chromatin, HeLa Cells, Humans, I2CT, Jurkat Cells, Lupus Erythematosus, Monneaux, Phosphorylation, Post-Translational, Protein Phosphatase 1, Protein Processing, Protein Transport, Recombinant Proteins, Ribonucleoprotein, RNA Splicing, Serine, Spliceosomes, Systemic, Team-Dumortier, Time Factors, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
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}
}
Monneaux Fanny, Hoebeke Johan, Sordet Christelle, Nonn Céline, Briand Jean-Paul, Maillère Bernard, Sibilia Jean, Muller Sylviane
Selective modulation of CD4+ Ŧ cells from lupus patients by a promiscuous, protective peptide analog Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 9, p. 5839–5847, 2005, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, CD4-Positive T-Lymphocytes, HLA-DR Antigens, Humans, I2CT, Interleukin-10, Lupus Erythematosus, Lymphocyte Activation, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear
@article{monneaux_selective_2005,
title = {Selective modulation of CD4+ Ŧ cells from lupus patients by a promiscuous, protective peptide analog},
author = {Fanny Monneaux and Johan Hoebeke and Christelle Sordet and Céline Nonn and Jean-Paul Briand and Bernard Maillère and Jean Sibilia and Sylviane Muller},
doi = {10.4049/jimmunol.175.9.5839},
issn = {0022-1767},
year = {2005},
date = {2005-11-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {9},
pages = {5839--5847},
abstract = {A peptide encompassing residues 131-151 of the spliceosomal U1-70K protein and its analog phosphorylated at Ser140 were synthesized as potential candidates for the treatment of patients with lupus. Studies in the MRL/lpr and (NZB x NZW)F1 lupus models have demonstrated that these sequences contain a CD4+ T cell epitope but administration of the phosphorylated peptide only ameliorates the clinical manifestations of treated MRL/lpr mice. Binding assays with soluble HLA class II molecules and molecular modeling experiments indicate that both peptides behave as promiscuous epitopes and bind to a large panel of human DR molecules. In contrast to normal T cells and T cells from non-lupus autoimmune patients, we found that PBMCs from 40% of lupus patients selected randomly and CFSE-labeled CD4+ T cells proliferate in response to peptide 131-151. Remarkably, however, we observed that phosphorylation of Ser140 prevents CD4+ T cells proliferation but not secretion of regulatory cytokines, suggesting a striking immunomodulatory effect of phosphorylated analog on lupus CD4+ T cells that was unique to patients. The analog might act as an activator of regulatory T cells or as a partial agonist of TCR.},
keywords = {Amino Acid Sequence, CD4-Positive T-Lymphocytes, HLA-DR Antigens, Humans, I2CT, Interleukin-10, Lupus Erythematosus, Lymphocyte Activation, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Monneaux Fanny, Parietti Véronique, Briand Jean-Paul, Muller Sylviane
Intramolecular Ŧ cell spreading in unprimed MRL/lpr mice: importance of the U1-70k protein sequence 131-151 Article de journal
Dans: Arthritis and Rheumatism, vol. 50, no. 10, p. 3232–3238, 2004, ISSN: 0004-3591.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Division, Female, I2CT, Immunization, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lymphocytes, Mice, Monneaux, Peptides, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear
@article{monneaux_intramolecular_2004,
title = {Intramolecular Ŧ cell spreading in unprimed MRL/lpr mice: importance of the U1-70k protein sequence 131-151},
author = {Fanny Monneaux and Véronique Parietti and Jean-Paul Briand and Sylviane Muller},
doi = {10.1002/art.20510},
issn = {0004-3591},
year = {2004},
date = {2004-10-01},
journal = {Arthritis and Rheumatism},
volume = {50},
number = {10},
pages = {3232--3238},
abstract = {OBJECTIVE: To analyze spontaneous T cell spreading against determinants of the U1-70K protein in young autoimmune MRL/lpr lupus mice, in comparison with the T cell spreading occurring in normal BALB/c mice immunized with peptide 131-151 of this protein.
METHODS: Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr mice and immunized BALB/c mice were tested for their ability to proliferate ex vivo in response to 18 overlapping peptides of the U1-70K spliceosomal protein, using assays for lymphocyte proliferation and secretion of interleukin-2.
RESULTS: The proliferative response to peptides of the U1-70K protein evolved rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were recognized by PBLs from 8-week-old autoimmune mice, whereas a different peptide was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the proliferative response was weak or negative when assessed with any of the test peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also recognized by PBLs generated in the BALB/c mice primed with peptide 131-151. We further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration of phosphorylated peptide 131-151 (called P140), which was shown previously to be protective, transiently abolished T cell intramolecular spreading to other regions of the 70K protein.
CONCLUSION: This is the first study to demonstrate that intramolecular T cell spreading effectively occurs in MRL/lpr mice with lupus, and that region 131-151 is important in the cascade of events observed in the murine lupus response. This sequence might originate a mechanism of tolerance spreading that leads to the beneficial effect observed in MRL/lpr mice after treatment with the phosphorylated peptide 131-151.},
keywords = {Animals, Cell Division, Female, I2CT, Immunization, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lymphocytes, Mice, Monneaux, Peptides, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Monneaux Fanny, Lozano José Manuel, Patarroyo Manuel E, Briand Jean-Paul, Muller Sylviane
T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice Article de journal
Dans: European Journal of Immunology, vol. 33, no. 2, p. 287–296, 2003, ISSN: 0014-2980.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animal, Animals, Autoantibodies, Autoantigens, Autoimmune Diseases, B-Lymphocytes, Cross Reactions, Disease Models, Female, HLA-DR Antigens, HLA-DR Serological Subtypes, HLA-DR1 Antigen, HLA-DR4 Antigen, Humans, I2CT, Immunization, Immunotherapy, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lupus Nephritis, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Protein Binding, Ribonucleoprotein, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear
@article{monneaux_t_2003,
title = {T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice},
author = {Fanny Monneaux and José Manuel Lozano and Manuel E Patarroyo and Jean-Paul Briand and Sylviane Muller},
doi = {10.1002/immu.200310002},
issn = {0014-2980},
year = {2003},
date = {2003-01-01},
journal = {European Journal of Immunology},
volume = {33},
number = {2},
pages = {287--296},
abstract = {Modifications of self antigens that occur during apoptosis might be involved in the generation of neo-antigens, which can break tolerance and induce autoimmunity. We have previously identified an epitope at residues 131-151 of the U1-70K snRNP protein, recognized by IgG antibodies and CD4+ T cells from at least two strains of lupus mice. With the aim of investigating the possible role of phosphorylation on the antigenicity of peptide 131-151 and to gain a better understanding of how this peptide can drive autoimmune response, we synthesized two peptides phosphorylated on Ser137 and 140, respectively. We show here that peptide P140 phosphorylated on Ser140 is recognized by both CD4+ T cells and antibodies from MRL/lpr mice. Furthermore, intravenous administration to lupus-prone MRL/lpr mice of P140 in saline (but not of the non-phosphorylated peptide) decreased proteinuria and anti-DNA antibody production, and significantly prolonged survival of treated mice. We further demonstrated that P140 is recognized by antibodies from lupus patients and binds to various HLA DR molecules, offering new hope for manipulating T cell response in humans.},
keywords = {Amino Acid Sequence, Animal, Animals, Autoantibodies, Autoantigens, Autoimmune Diseases, B-Lymphocytes, Cross Reactions, Disease Models, Female, HLA-DR Antigens, HLA-DR Serological Subtypes, HLA-DR1 Antigen, HLA-DR4 Antigen, Humans, I2CT, Immunization, Immunotherapy, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lupus Nephritis, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Protein Binding, Ribonucleoprotein, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Dumortier H, Steiner G, Briand J P, Muller S
Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice Article de journal
Dans: International Immunology, vol. 13, no. 9, p. 1155–1163, 2001, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear
@article{monneaux_murine_2001,
title = {Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice},
author = {F Monneaux and H Dumortier and G Steiner and J P Briand and S Muller},
doi = {10.1093/intimm/13.9.1155},
issn = {0953-8178},
year = {2001},
date = {2001-01-01},
journal = {International Immunology},
volume = {13},
number = {9},
pages = {1155--1163},
abstract = {(NZB x NZW)F(1) and MRL/Fas(lpr) lupus mice present a similar phenotype with a spectrum of autoantibodies associated with very severe nephritis. It is thought, however, that in contrast to other lupus-prone mice such as MRL/Fas(lpr) mice, (NZB x NZW)F(1) mice do not generate autoantibodies to ribonucleoproteins (RNP) Sm/RNP. In this study, we demonstrate that contrary to previous reports, the autoimmune response directed against Sm/RNP antigens also occurs in NZB x NZW mice. CD4(+) T cells from unprimed 10-week-old NZB x NZW mice proliferate and secrete IL-2 in response to peptide 131-151 of the U1-70K protein, which is known to contain a T(h) epitope recognized by CD4(+) T cells from MRL/Fas(lpr) mice. Peptide 131-151, which was found to bind I-A(k) and I-E(k) class II MHC molecules, also bound both I-A(d) and I-E(d) molecules. This result led us to also re-evaluate longitudinally the anti-Sm/RNP antibody response in NZB x NZW mice. We found that 25-week-old mice do produce antibodies reacting with several small nuclear and heterogeneous nuclear (hn) RNP proteins, such as SmD1, U1-70K and hnRNP A2/B1 proteins. The fine specificity of these antibodies was studied with overlapping synthetic peptides. The same antigenically positive and negative peptides were characterized in MRL/Fas(lpr) and NZB x NZW mice in the three proteins. This new finding can help to understand the mechanisms involved in the development of the anti-Sm/RNP antibody response and, particularly, the role played by non-MHC genes in this autoimmune response.},
keywords = {Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Briand J P, Muller S
Dans: European Journal of Immunology, vol. 30, no. 8, p. 2191–2200, 2000, ISSN: 0014-2980.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Motifs, Animals, Antigen-Presenting Cells, Autoimmunity, B-Lymphocytes, CD4-Positive T-Lymphocytes, Epitopes, Female, I2CT, Inbred BALB C, Inbred CBA, Inbred MRL lpr, Lupus Vulgaris, Lymphocyte Activation, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, T-Lymphocyte, Team-Dumortier, U1 Small Nuclear
@article{monneaux_b_2000,
title = {B and Ŧ cell immune response to small nuclear ribonucleoprotein particles in lupus mice: autoreactive CD4(+) Ŧ cells recognize a Ŧ cell epitope located within the RNP80 motif of the 70K protein},
author = {F Monneaux and J P Briand and S Muller},
doi = {10.1002/1521-4141(2000)30:8<2191::AID-IMMU2191>3.0.CO;2-R},
issn = {0014-2980},
year = {2000},
date = {2000-08-01},
journal = {European Journal of Immunology},
volume = {30},
number = {8},
pages = {2191--2200},
abstract = {Systemic lupus erythematosus is characterized by the presence of high titers of autoantibodies reacting with various components of the U1 small nuclear ribonucleoprotein particle (snRNP). It has been suggested that these antibodies are produced by an antigen-driven mechanism under the dependence of antigen-specific T cells. To investigate the role of T cell help in this process, we sought, with 20 overlapping peptides, the Th epitopes on the U1-70K snRNP in unprimed H-2(k) MRL / lpr lupus mice and immunized CBA normal mice. The peptide 131 - 151 was recognized by both IgG autoantibodies and CD4(+) T cells from 7 - 9-week-old MRL / lpr mice. In this test, antigen-presenting cells (APC) from MRL / lpr mice were required; APC from naive CBA mice failed to stimulate CD4(+) cells from MRL / lpr mice. The potential role of MRL / lpr B cells as APC, the expression of MHC class II molecules at their surface and their activation state (expression of CD69, CD80 / B7-1 and CD86 / B7-2 molecules) were studied. Peptide 131 - 151 bound both I-A(k) and I-E(k) class II molecules and favored an IL-2-positive T cell response but not IFN-gamma, IL-6 and IL-10 secretion. Segment 131 - 151 is localized within the RNP80 motif and contains residues that are highly conserved in many nuclear, nucleolar and cytoplasmic RNA binding proteins.},
keywords = {Amino Acid Motifs, Animals, Antigen-Presenting Cells, Autoimmunity, B-Lymphocytes, CD4-Positive T-Lymphocytes, Epitopes, Female, I2CT, Inbred BALB C, Inbred CBA, Inbred MRL lpr, Lupus Vulgaris, Lymphocyte Activation, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, T-Lymphocyte, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Abbal M, Fort M, Briand J P, Cantagrel A, Muller S
MHC class II gene associations with autoantibodies to U1A and SmD1 proteins Article de journal
Dans: International Immunology, vol. 11, no. 2, p. 249–257, 1999, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western
@article{dumortier_mhc_1999,
title = {MHC class II gene associations with autoantibodies to U1A and SmD1 proteins},
author = {H Dumortier and M Abbal and M Fort and J P Briand and A Cantagrel and S Muller},
doi = {10.1093/intimm/11.2.249},
issn = {0953-8178},
year = {1999},
date = {1999-01-01},
journal = {International Immunology},
volume = {11},
number = {2},
pages = {249--257},
abstract = {Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently present in the serum of patients with systemic rheumatic diseases, and have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studied immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patients' sera selected on the basis of their antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and antibodies reacting with U1A and SmD1 antigens. This first study reporting an association between autoantibodies reacting with U1A and SmD1 proteins (and peptides of these proteins), and immunogenetic markers suggest that the production of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with distinct MHC class II alleles.},
keywords = {Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Gunnewiek J Klein, Roussel J P, van Aarssen Y, Briand J P, van Venrooij W J, Muller S
Dans: Nucleic Acids Research, vol. 26, no. 23, p. 5486–5491, 1998, ISSN: 0305-1048.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers
@article{dumortier_at_1998,
title = {At least three linear regions but not the zinc-finger domain of U1C protein are exposed at the surface of the protein in solution and on the human spliceosomal U1 snRNP particle},
author = {H Dumortier and J Klein Gunnewiek and J P Roussel and Y van Aarssen and J P Briand and W J van Venrooij and S Muller},
doi = {10.1093/nar/26.23.5486},
issn = {0305-1048},
year = {1998},
date = {1998-12-01},
journal = {Nucleic Acids Research},
volume = {26},
number = {23},
pages = {5486--5491},
abstract = {No structural information on U1C protein either in its free state or bound to the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle is currently available. Using rabbit antibodies raised against a complete set of 15 U1C overlapping synthetic peptides (16-30 residues long) in different immunochemical tests, linear regions exposed at the surface of free and U1 snRNP-bound U1C were identified. Epitopes within at least three regions spanning residues 31-62, 85-103 and 116-159 were recognized on free and plastic-immobilized recombinant human U1C expressed in Escherichia coli, on in vitro translated U1C protein and on U1C bound to the U1 snRNP particle present in HeLa S100 extract. Using a zinc affinity labeling method, we further showed that the N-terminal U1C peptide containing a zinc-finger motif (peptide 5-34) effectively binds65Zn2+. The N-terminal region of U1C, which is functional in U1 snRNP assembly, is apparently not located at the surface of the U1 snRNP particle.},
keywords = {Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
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}
}
Halimi H, Dumortier H, Briand J P, Muller S
Comparison of two different methods using overlapping synthetic peptides for localizing linear B cell epitopes in the U1 snRNP-C autoantigen Article de journal
Dans: Journal of Immunological Methods, vol. 199, no. 1, p. 77–85, 1996, ISSN: 0022-1759.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Humans, I2CT, Lupus Erythematosus, Molecular Sequence Data, Peptides, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear
@article{halimi_comparison_1996,
title = {Comparison of two different methods using overlapping synthetic peptides for localizing linear B cell epitopes in the U1 snRNP-C autoantigen},
author = {H Halimi and H Dumortier and J P Briand and S Muller},
doi = {10.1016/s0022-1759(96)00171-8},
issn = {0022-1759},
year = {1996},
date = {1996-11-01},
journal = {Journal of Immunological Methods},
volume = {199},
number = {1},
pages = {77--85},
abstract = {We have compared the performances of two different approaches using overlapping synthetic peptides to identify the location of linear epitopes of the U1 snRNP-C autoantigen. The first method was based on the use of 15 overlapping peptides (16-30 residue-long) synthesized using conventional Fmoc chemistry, removed from the resin by a standard cleavage procedure, and tested by ELISA after direct coating to polyvinyl microtiter plates. The second approach used a commercial kit (SPOT) to synthesize 75 overlapping decapeptides on cellulose membrane which were assayed by a direct immunoenzymatic test. Both standard and SPOTscan methods were evaluated with antibodies raised in rabbits against synthetic peptides of U1C and sera from patients with autoimmune diseases. In addition to inherent problems linked to the SPOT synthesis (in particular the impossibility of checking the quality of peptides), a number of limitations in the SPOTscan method were identified (e.g. a certain lack of sensitivity and, in one case, the complete lack of peptide reactivity due to the removal of charged end groups at both extremities). However, we found no background with sera from autoimmune patients in the SPOTscan and the antigenic maps obtained using the two approaches generally agreed. This study shows that the SPOTscan approach represents a simple, relatively non expensive and rapid method for initial screening to identify candidate sequences that may be dominant linear epitopes in a protein. Subsequent analysis and controls should include the preparation of conventionally synthesized peptides for formal immunochemical investigations.},
keywords = {Amino Acid Sequence, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Humans, I2CT, Lupus Erythematosus, Molecular Sequence Data, Peptides, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}