Response of MRL/Mp-+/+ mice to mouse Sm: non-H-2-linked genes determine T cell recognition.
In normal mouse strains, the T cell proliferative response to the nuclear autoantigen Sm is under MHC-linked Ir gene control. Autoimmune MRL/Mp-+/+ (+/+) mice, which spontaneously make anti-Sm antibodies, have the nonresponder H-2k MHC genotype, yet their T cells respond to mouse Sm. In the present study, we have used Sm-reactive continuous T cell lines to show that the Sm responsiveness of +/+ T cells is not due to aberrancy of the Iak molecules expressed on +/+ antigen-presenting cells. Additionally, the failure of normal Iak mouse strains to respond to mouse Sm could not be attributed to the influence of suppressor cells. Therefore, the response of +/+ mice to mouse Sm is probably due to the development of an abnormal repertoire of T cells capable of recognizing self-antigens in the context of Ia. Analyses of F1 hybrid and backcross mice indicated that their responsiveness was inherited in a dominant manner, probably as a single gene not linked to H-2. Further investigation of this gene and its mode of action may lead to increased understanding of the mechanisms of spontaneous autoimmunity in SLE mice.
Bernard
N F
NF
Eisenberg
R A
RA
Cohen
P L
PL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D001324:Autoantigens; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains / Q000276:immunology*; D011817:Rabbits; D017411:Ribonucleoproteins, Small Nuclear; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055517:snRNP Core Proteins
D000941:Antigens; D001324:Autoantigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins