The level of peptide-MHC complex determines the susceptibility to autoimmune diabetes: studies in HEL transgenic mice

Eur J Immunol. 2001 Dec;31(12):3453-9. doi: 10.1002/1521-4141(200112)31:12<3453::aid-immu3453>;2-h.


We report a mouse model for the spontaneous development of autoimmune diabetes: the 3A9 T cell receptor (TCR) transgenic mouse, which contains T cells that recognize the 52 - 61 family of hen egg-white lysozyme (HEL) peptides in the context of MHC class II I-A(k) molecules, was bred to the ILK3 mouse, that expresses HEL protein via the rat insulin promoter (RIP). Despite partial tolerance of 3A9 T cells in ILK3 mice, spontaneous diabetes developed in 64 % of 3A9xILK3 mice by 20 weeks of age. We provide evidence that APC from peri-pancreatic nodes have a large content of peptide-MHC complex and stimulate 3A9 T cells. We also report that cross presentation of HEL from beta cells to APC is 26-fold more efficient than presentation of soluble HEL. We previously reported on a biochemical margin of safety, based on the observation that activation of naive 3A9 T cells required 100-fold more peptide-MHC complexes than required for deletion of 3A9 thymocytes. We speculate that the high local density of autologous peptide-MHC complexes can be a determining factor that leads to the activation of autoreactive CD4 T cells and, consequently, to the development of autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Diabetes Mellitus, Type 1 / etiology*
  • Disease Susceptibility
  • Histocompatibility Antigens / metabolism*
  • Islets of Langerhans / immunology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Muramidase / immunology*
  • T-Lymphocytes / physiology


  • Histocompatibility Antigens
  • hen egg lysozyme
  • Muramidase