Allelic inclusion of T cell receptor alpha genes poses an autoimmune hazard due to low-level expression of autospecific receptors

Immunity. 1998 May;8(5):563-70. doi: 10.1016/s1074-7613(00)80561-0.


Organ-specific autoimmune disease can be caused by alphabeta T cells that have escaped self-tolerance induction. Here we show that one of the causes of escape from self-tolerance is the coexpression of two different T cell receptors by the same cell, which can occur in up to 30% of all T cells in normal mice and can lead to low-level surface expression of an autospecific TCR. We found that double receptor-expressing T cells can escape tolerance even to ubiquitously expressed antigens but can nevertheless induce autoimmune diabetes when the relevant protein is expressed in pancreatic tissue. Such diabetogenic T cells are absent, however, among T cells expressing the autospecific TCR as the sole receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Autoimmunity / genetics*
  • CD4-Positive T-Lymphocytes / immunology*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Insulin / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Pancreas / immunology
  • Pancreas / metabolism
  • Promoter Regions, Genetic
  • Rats
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Self Tolerance / genetics


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Insulin
  • Receptors, Antigen, T-Cell, alpha-beta