Development and function of autospecific dual TCR+ T lymphocytes

Recent studies have challenged the long held concept that each T lymphocyte expresses on its surface only a single, unique alpha beta TCR. Dual TCR+ T cells have been recognized, however, their origin and potential to escape screening for self-reactivity remain obscure. We now report the thymic gene ration of dual alpha beta TCR+ T cells in the H-2D(b)/H-Y-specific TCR tran sgenic (Tg) mouse. Dual TCR+ thymocytes were positively selected less effic iently than single TCR+ thymocytes, although a subset attained maturity. Im portantly, when TCR Tg mice were bred onto a negatively selecting backgroun d, auto-specific cells survived central deletion and matured as CD4(+) dual TCR+ cells. These cells were autoreactive when CD8 expression was restored . The existence of autospecific, dual TCR+ T cells may have implications fo r the maintenance of self tolerance.