Allelic exclusion at the T-cell receptor α chain locus is incomplete resulting in the generation oft 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, M. and Lanzavecchia, A. (1993) Science 262, 422-424; Heath, W. R. and 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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Aug 20 1996|
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