Allelic inclusion of T cell receptor alpha genes poses an autoimmune hazard due to low-level expression of autospecific receptors.
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.
Sarukhan
A
A
Institut Necker, INSERM 373, Paris, France.
Garcia
C
C
Lanoue
A
A
von Boehmer
H
H
D000483:Alleles; D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007328:Insulin / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics*; D017634:Self Tolerance / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007328:Insulin; D016693:Receptors, Antigen, T-Cell, alpha-beta