Exclusion and inclusion of TCRα proteins during T cell development in TCR-transgenic and normal mice

Allelic exclusion of immune receptor genes (and molecules) is incompletely understood. With regard to TCRαβ lineage T cells, exclusion at the tcr-b, but not tcr-a, locus seems to be strictly controlled at the locus rearrangement level. Consequently, while nearly all developing TCRαβ thymocytes express a single TCRβ protein, many thymocytes rearrange and express two different TCRα chains and, thus, display two αβTCRs on the cell surface. Of interest, the number of such deal TCR-expressing cells is appreciably lower among the mature T cells. To understand the details of TCR chain regulation at various stages of T cell development, we analyzed TCR expression in mice transgenic for two rearranged αβTCR. We discovered that in such TCR double-transgenic (TCRdTg) mice peripheral T cells were functionally monospeciflc. Molecularly, this monospecificity was due to TCRα exclusion: one transgenic TCRα protein was selectively down-regulated from the thymocyte and T cell surface. In searching for the mechanism(s) governing this selective TCRα down-regulation, we present evidence for the role of protein tyrosine kinase signaling and coreceptor involvement. This mechanism may be operating in normal thymocytes.