The association of MHC with autoimmune diseases: Understanding the pathogenesis of autoimmune diabetes

Abstract

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.