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

Tomasz Zal, Siegfried Weiss, Andrew Mellor, Brigitta Stockinger

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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 languageEnglish (US)
Pages (from-to)9102-9107
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
Publication statusPublished - Aug 20 1996


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