DURING T-cell development, site-specific DNA rearrangements mediating assembly of β- and α-chain genes of the T-cell receptor (TCR) are developmentally ordered1,2. In particular, assembly and expression of a complete β-chain gene blocks further rearrangements at the β-locus (a process referred to as allelic exclusion)3 and drives the generation and expansion of CD4+ 8+ cells4,5. Although the mechanism used by TCRβ chains to deliver such signals is unknown, studies in transgenic animals have suggested that the lymphocyte-specific protein tyrosine kinase p56lck may impinge on a similar signalling pathway6. The hypothesis that TCRβ chains deliver intracellular signals via p56lck makes an explicit prediction: that interference with p56lck function will mitigate the effects of a simultaneously expressed TCRβ chain. Here we confirm this prediction through examination of allelic exclusion in mice expressing both a functional TCRβ chain transgene and a catalytically inactive form of p56lck.
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