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

Clin Immunol Immunopathol. 1998 Jan;86(1):3-10. doi: 10.1006/clin.1997.4449.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Clonal Deletion
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / immunology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Disease Susceptibility
  • Genes, MHC Class II
  • HLA-D Antigens / genetics
  • HLA-D Antigens / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology*
  • Mice
  • Mice, Inbred NOD
  • Models, Immunological
  • Protein Binding
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocyte Subsets / immunology*


  • HLA-D Antigens
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell, alpha-beta