Protein tyrosine kinase p56^lck controls allelic exclusion of T-cell receptor β-chain genes

DURING T-cell development, site-specific DNA rearrangements mediating assembly of β- and α-chain genes of the T-cell receptor (TCR) are developmentally ordered^1,2. 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⁺ cells^4,5. 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 p56^lck may impinge on a similar signalling pathway⁶. The hypothesis that TCRβ chains deliver intracellular signals via p56^lck makes an explicit prediction: that interference with p56^lck 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 p56^lck.