Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function

Allelic exclusion at the T-cell receptor alpha chain locus is incomplete resulting in the generation of T cells that express two T-cell receptors, The potential involvement of such T cells in autoimmunity has been suggested [Padovan, E,, Casorati, G,, Dellabona, P,, Meyer, S,, Brockhaus, hi, & Lanzavecchia, A, (1993) Science 262, 422-424; Heath, W. R. & Miller, J, F, A, P, (1993) J, Exp. Med. 178, 1807-1811], Here we show that expression of a second T-cell receptor can rescue T cells with autospecific receptors from thymic deletion and allow their exit into the periphery, Dual receptor T cells, created by constitutive expression of two transgenic T-cell receptors on a Rag1(-/-) background, are tolerant to self by maintaining low levels of autospecific receptor, but self-reactive effector function (killing) can be induced through activation via the second receptor, This opens the possibility that T cells carrying two receptors in the periphery of normal individuals contain putatively autoreactive cells that could engage in autoimmune effector functions after recognition of an unrelated environmental antigen.