Anderson S J, Abraham K M, Nakayama T, Singer A, Perlmutter R M
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
EMBO J. 1992 Dec;11(13):4877-86. doi: 10.1002/j.1460-2075.1992.tb05594.x.
The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.
T细胞受体（TCR）α链和β链的可变区基因是通过单独的种系元件的体细胞重组而组装的。在胸腺细胞发育过程中，基因重排呈现出有序的进展，β链形成先于α链，并且存在等位基因排斥现象，即每个细胞只包含一个功能性β链重排。尽管有大量证据支持各个基因座是独立调控的观点，但可能参与控制TCR基因重组的信号分子仍未明确。在此我们报告，淋巴细胞特异性蛋白酪氨酸激酶p56lck在发育中的胸腺细胞中过表达时，会导致Vβ-Dβ重排减少，同时允许其他TCR基因片段正常并列。我们的数据支持一种模型，即p56lck活性影响一个通常允许β链基因座发生等位基因排斥的信号传导过程。
