Molecular targeting of islet autoantigens

Immunity. 2010 Apr 23;32(4):446-56. doi: 10.1016/j.immuni.2010.04.008.


Type 1 diabetes of man and animal models results from immune-mediated specific beta cell destruction. Multiple islet antigens are targets of autoimmunity and most of these are not beta cell specific. Immune responses to insulin appear to be essential for the development of diabetes of the NOD mouse. In this review, we will emphasize the unusual manner in which selected autoantigenic peptides (particularly the recently discovered target of BDC2.5 T cells [chromagranin A]) are presented and recognized by autoreactive CD4(+) T cell receptors. We hypothesize that "unusual" structural interactions of specific trimolecular complexes (MHC class II, peptide, and T cell receptors) are fundamental to the escape from the thymus of autoreactive T cells able to cause type 1 diabetes.

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Islets of Langerhans / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology


  • Autoantigens
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell