Do the Peptide-Binding Properties of Diabetogenic Class II Molecules Explain Autoreactivity?

Curr Opin Immunol. 2008 Feb;20(1):105-10. doi: 10.1016/j.coi.2007.10.007. Epub 2007 Dec 21.

Abstract

One seminal aspect in autoimmune diabetes is antigen presentation of beta cell antigens by the diabetes-propensity class II histocompatibility molecules. The binding properties of I-Ag7 molecules are reviewed here and an emphasis is placed on their selection of peptides with a highly specific sequence motif, in which one or more acidic amino acids are found at the carboxy end interacting at the P9 anchoring site of I-Ag7. The reasons for the central role of I-Ag7 in the autoimmune response are analyzed. The insulin B chain segment 9-23 is a hot spot for T cell selection and a striking example of a weak MHC binding peptide that triggers autoreactivity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation*
  • Autoimmunity*
  • Diabetes Mellitus, Type 1 / immunology*
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Insulin / chemistry
  • Insulin / immunology
  • Mice
  • Peptides / chemistry
  • Peptides / immunology*
  • T-Lymphocytes / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Insulin
  • Peptides