T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MRL/Ipr mice

被引:112
作者
Monneaux, F
Lozano, JM
Patarroyo, ME
Briand, JP
Muller, S
机构
[1] CNRS, Inst Biol Mol & Cellulaire, UPR 9021, F-67000 Strasbourg, France
[2] Univ Nacl Colombia, Fdn Inst Immunol Colombia, Santafe de Bogota, Colombia
关键词
snRNP protein; Lupus mouse; B and T cell epitope; phosphorylated peptide; tolerance;
D O I
10.1002/immu.200310002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Ser(137) and (140), respectively. We show here that peptide P140 phosphorylated on Ser(140) is recognized by both CD4(+) T cells and antibodies from MRL/Ipr mice. Furthermore, intravenous administration to lupus-prone MRL/Ipr 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.
引用
收藏
页码:287 / 296
页数:10
相关论文
共 58 条
[1]  
Amoura Z, 1999, ARTHRITIS RHEUM, V42, P833, DOI 10.1002/1529-0131(199905)42:5<833::AID-ANR1>3.0.CO
[2]  
2-T
[3]  
CalvoCalle JM, 1997, J IMMUNOL, V159, P1362
[4]   Cleavage by granzyme B is strongly predictive of autoantigen status: Implications for initiation of autoimmunity [J].
Casciola-Rosen, L ;
Andrade, F ;
Ulanet, D ;
Wong, WB ;
Rosen, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (06) :815-825
[5]   AUTOANTIGENS TARGETED IN SYSTEMIC LUPUS-ERYTHEMATOSUS ARE CLUSTERED IN 2 POPULATIONS OF SURFACE-STRUCTURES ON APOPTOTIC KERATINOCYTES [J].
CASCIOLAROSEN, LA ;
ANHALT, G ;
ROSEN, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (04) :1317-1330
[6]   Recent developments in the understanding of antinuclear autoantibodies [J].
Casiano, CA ;
Tan, EM .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 1996, 111 (04) :308-313
[7]   ANTIGEN ANALOG MAJOR HISTOCOMPATIBILITY COMPLEXES ACT AS ANTAGONISTS OF THE T-CELL RECEPTOR [J].
DEMAGISTRIS, MT ;
ALEXANDER, J ;
COGGESHALL, M ;
ALTMAN, A ;
GAETA, FCA ;
GREY, HM ;
SETTE, A .
CELL, 1992, 68 (04) :625-634
[8]   Post-translational protein modifications in antigen recognition and autoimmunity [J].
Doyle, HA ;
Mamula, MJ .
TRENDS IN IMMUNOLOGY, 2001, 22 (08) :443-449
[9]   Prevention of systemic lupus erythematosus-like disease in (NZBxNZW)F1 mice by treating with CDR1-and CDR3-based peptides of a pathogenic autoantibody [J].
Eilat, E ;
Zinger, H ;
Nyska, A ;
Mozes, E .
JOURNAL OF CLINICAL IMMUNOLOGY, 2000, 20 (04) :268-278
[10]   ANTAGONISM OF SUPERANTIGEN-STIMULATED HELPER T-CELL CLONES AND HYBRIDOMAS BY ALTERED PEPTIDE LIGAND [J].
EVAVOLD, BD ;
SLOANLANCASTER, J ;
ALLEN, PM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2300-2304