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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / metabolism
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Autoantigens / immunology
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Autoantigens / isolation & purification
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Autoantigens / metabolism*
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Binding Sites, Antibody
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Binding, Competitive / immunology
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Cells, Cultured
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Disease Susceptibility / immunology
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Epitopes, B-Lymphocyte / analysis
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / isolation & purification
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Epitopes, T-Lymphocyte / metabolism
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / isolation & purification
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Histocompatibility Antigens Class II / metabolism*
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Histones / administration & dosage
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Histones / immunology
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Histones / isolation & purification
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Immunization
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / metabolism
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Inbred MRL lpr
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Molecular Sequence Data
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Peptide Fragments / immunology*
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Peptide Fragments / isolation & purification
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Peptide Fragments / metabolism*
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Protein Binding / immunology
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Ribosomal Proteins / administration & dosage
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Ribosomal Proteins / immunology
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Ribosomal Proteins / isolation & purification
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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beta 2-Microglobulin / administration & dosage
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beta 2-Microglobulin / immunology
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beta 2-Microglobulin / isolation & purification
Substances
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Antibodies, Monoclonal
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Autoantigens
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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Histones
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I-Ak antigen
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I-E-antigen
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Peptide Fragments
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Ribosomal Proteins
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beta 2-Microglobulin