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

Suh, CH; Freed, JH; Cohen, PL
Journal of immunology (Baltimore, Md. : 1950), 170(4):2229-2235, 2003
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
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.
MeSH terms
Amino Acid SequenceAnimalsAntibodies, Monoclonal/metabolismAutoantigens/immunologyAutoantigens/isolation & purificationAutoantigens/metabolism*Binding Sites, AntibodyBinding, Competitive/immunologyCells, CulturedDisease Susceptibility/immunologyEpitopes, B-Lymphocyte/analysisEpitopes, T-Lymphocyte/immunologyEpitopes, T-Lymphocyte/isolation & purificationEpitopes, T-Lymphocyte/metabolismHistocompatibility Antigens Class II/immunologyHistocompatibility Antigens Class II/isolation & purificationHistocompatibility Antigens Class II/metabolism*Histones/administration & dosageHistones/immunologyHistones/isolation & purificationImmunizationLupus Erythematosus, Systemic/immunology*Lupus Erythematosus, Systemic/metabolismLymphocyte Activation/immunologyMiceMice, Inbred C3HMice, Inbred C57BLMice, Inbred MRL lprMolecular Sequence DataPeptide Fragments/immunology*Peptide Fragments/isolation & purificationPeptide Fragments/metabolism*Protein Binding/immunologyRibosomal Proteins/administration & dosageRibosomal Proteins/immunologyRibosomal Proteins/isolation & purificationSpleen/cytologySpleen/immunologyT-Lymphocyte Subsets/immunology*T-Lymphocyte Subsets/metabolism*beta 2-Microglobulin/administration & dosagebeta 2-Microglobulin/immunologybeta 2-Microglobulin/isolation & purification
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Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
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