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, 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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Division of Molecular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom.
Weiss
S
S
Mellor
A
A
Stockinger
B
B
D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology*; D003182:Complement C5 / Q000235:genetics; D003433:Crosses, Genetic; D018398:Homeodomain Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D003182:Complement C5; D018398:Homeodomain Proteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein