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

First Author  Zal T Year  1996
Journal  Proc Natl Acad Sci U S A Volume  93
Issue  17 Pages  9102-7
PubMed ID  8799161 Mgi Jnum  J:151753
Mgi Id  MGI:4355142 Doi  10.1073/pnas.93.17.9102
Citation  Zal T, et al. (1996) Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function. Proc Natl Acad Sci U S A 93(17):9102-7
abstractText  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, M. & 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 selfreactive 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.
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