Dual-receptor T cells expressing one self-restricted TCR.
During thymic development, T cells rearrange and express genes encoding clonotypic T-cell receptors (TCR), and undergo selective events involving interactions between TCR and thymic major histocompatibility complex (MHC) molecules. Recent studies indicate that up to 30% of peripheral T cells may express two TCR, that both TCR on these cells are functional, and that dual-specific T cells can promote autoimmunity. Here we demonstrate that dual-receptor T cells are readily generated in class II-deficient (class II-) mice expressing the class II-restricted AND TCR transgene (TCRtg). While this TCRtg is unable to promote positive selection in class II- mice, T cells arise in class II-TCR+tg mice by co-expressing non-transgenic endogenous TCR that permit positive selection on class I molecules. Our findings indicate that when a rearranged TCR fails to promote positive selection on self MHC molecules, expression of a second receptor can rescue the developing T cell. Accordingly, many dual-receptor T cells may actually be mono-specific in vivo, possessing only one self MHC-restricted TCR, and therefore should not require unique regulatory controls to prevent autoreactivity.
Smiley
S T
ST
Department of Cancer Biology, Harvard School of Public Health, Boston, USA.
Grusby
M J
MJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003574:Cytochrome c Group / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*
D003574:Cytochrome c Group; D016693:Receptors, Antigen, T-Cell, alpha-beta