T cell reactivity to MHC class II-bound self peptides in systemic lupus erythematosus-prone MRL/lpr mice

J Immunol. 2003 Feb 15;170(4):2229-35. doi: 10.4049/jimmunol.170.4.2229.

Abstract

The epitopes recognized by pathogenic T cells in systemic autoimmune disease remain poorly defined. Certain MHC class II-bound self peptides from autoimmune MRL/lpr mice are not found in eluates from class II molecules of MHC-identical C3H mice. Eleven of 16 such peptides elicited lymph node cell and spleen cell T cell proliferation in both MRL/lpr (stimulation index = 2.03-5.01) and C3H mice (stimulation index = 2.03-3.75). IL-2 and IFN-gamma production were detected, but not IL-4. In contrast to what was seen after immunization, four self peptides induced spleen cell proliferation of T cells from naive MRL/lpr, but not from C3H and C57BL/6.H2(k), mice. These peptides were derived from RNA splicing factor SRp20, histone H2A, beta(2)-microglobulin, and MHC class II I-A(k)beta. The first three peptides were isolated from I-E(k) molecules and the last peptide was bound to I-A(k). T cell responses, evident as early as 1 mo of age, depended on MHC class II binding motifs and were inhibited by anti-MHC class II Abs. Thus, although immunization can evoke peripheral self-reactive T cells in normal mice, the presence in MRL/lpr mice of spontaneous T cells reactive to certain MHC-bound self peptides suggests that these T cells actively participate in systemic autoimmunity. Peptides eluted from self MHC class II molecules may yield important clues to T cell epitopes in systemic autoimmunity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Autoantigens / immunology
  • Autoantigens / isolation & purification
  • Autoantigens / metabolism*
  • Binding Sites, Antibody
  • Binding, Competitive / immunology
  • Cells, Cultured
  • Disease Susceptibility / immunology
  • Epitopes, B-Lymphocyte / analysis
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / isolation & purification
  • Epitopes, T-Lymphocyte / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / isolation & purification
  • Histocompatibility Antigens Class II / metabolism*
  • Histones / administration & dosage
  • Histones / immunology
  • Histones / isolation & purification
  • Immunization
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism*
  • Protein Binding / immunology
  • Ribosomal Proteins / administration & dosage
  • Ribosomal Proteins / immunology
  • Ribosomal Proteins / isolation & purification
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • beta 2-Microglobulin / administration & dosage
  • beta 2-Microglobulin / immunology
  • beta 2-Microglobulin / isolation & purification

Substances

  • Antibodies, Monoclonal
  • Autoantigens
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Histones
  • I-Ak antigen
  • I-E-antigen
  • Peptide Fragments
  • Ribosomal Proteins
  • beta 2-Microglobulin