Susceptible MHC Alleles, Not Background Genes, Select an Autoimmune T Cell Reactivity

J Clin Invest. 2003 Sep;112(6):902-14. doi: 10.1172/JCI18337.

Abstract

To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7 MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.

Publication types

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

MeSH terms

  • Alleles*
  • Animals
  • Autoantigens / immunology
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / physiology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Female
  • Haplotypes
  • Hybridomas / cytology
  • Hybridomas / immunology
  • Hybridomas / metabolism
  • Major Histocompatibility Complex / genetics*
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism

Substances

  • Autoantigens
  • Receptors, Antigen, T-Cell