The association of MHC with autoimmune diseases: understanding the pathogenesis of autoimmune diabetes.
The current paradigm of MHC and disease association is efficient binding of autoantigens by disease-associated MHC molecules leading to a T cell-mediated immune response and resultant autoimmune sequelae. Data presented here offer a different model for this association of MHC with autoimmune diabetes. This new explanation suggests that the association of MHC with autoimmunity results from "altered" thymic selection in which high-affinity self-reactive (potentially autoreactive) T cells escape negative selection. This model offers an explanation for the requirement of homozygous MHC class II expression in NOD mice (and in man) in susceptibility to IDDM.
Ridgway
W M
WM
Department of Medicine, Stanford University School of Medicine, California 94305-5111, USA.
Fathman
C G
CG
D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D017637:Clonal Deletion; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018448:Models, Immunological; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta