H-2-linked Ir gene control of T cell recognition of the Sm nuclear autoantigen and the aberrant response of autoimmune MRL/Mp-+/+ mice.
We have examined T cell recognition of the nuclear autoantigen Sm. Rabbit Sm-primed cells from autoimmune MRL/Mp-+/+ (+/+) mice and from all normal strains tested were able to proliferate to rabbit Sm in vitro. In contrast, the reactivity of normal strains to Sm of murine origin was genetically restricted; only H-2f strains B10.M and A.CA, and H-2s strains B10.S and A.SW could recognize mouse Sm, suggesting that responsiveness to mouse Sm was under the control of H-2-linked Ir genes. Although five Iak-bearing normal strains (B10.A, B10.A(2R), B10.BR, A/Sn, and CBA) did not recognize mouse Sm, autoimmune +/+ (Iak) mice were responders. The responsiveness of the +/+ mice to Sm was probably not due to differences in their Iak region, compared with other strains, because the Iak region of normal strains and the autoimmune +/+ strain were indistinguishable by interstrain MLC, immune response gene product function, and recognition by anti-Iak mAb. Inhibition of Sm-induced proliferation by mAb demonstrated that T cells from autoimmune +/+ mice, responder normal strains, and nonresponder normal strains recognized rabbit and mouse Sm in the context of I region-encoded products. The T cell response to Sm antigen in normal mice is therefore Ia region restricted and, for the murine antigen, under Ir gene control. Autoimmune mice that spontaneously make anti-Sm antibodies (+/+) also perceive Sm in an Ia-restricted manner, but their responder status abrogates H-2-linked Ir gene control.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000941:Antigens / Q000032:analysis / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D001667:Binding, Competitive; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D011817:Rabbits; D017411:Ribonucleoproteins, Small Nuclear; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D055517:snRNP Core Proteins
D000911:Antibodies, Monoclonal; D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D006183:H-2 Antigens; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins