T cell reactivity to MHC class II-bound self peptides in systemic lupus erythematosus-prone MRL/lpr mice.
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.
Suh
Chang-Hee
CH
Division of Rheumatology, Department of Medicine, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Freed
John H
JH
Cohen
Philip L
PL
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000032:analysis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006657:Histones / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D012269:Ribosomal Proteins / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D006657:Histones; C111388:I-Ak antigen; C024138:I-E-antigen; D010446:Peptide Fragments; D012269:Ribosomal Proteins; D001613:beta 2-Microglobulin