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 alpha beta T cells that have escaped self-tolerance induction. Here we show that one of t he causes of escape from self-tolerance is the coexpression of two dif ferent 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 expre ssion 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 prot ein is expressed in pancreatic tissue. Such diabetogenic T cells are a bsent, however, among T cells expressing the autospecific TCR as the s ole receptor.