Erman Batu, Feigenbaum Lionel, Coligan John E, Singer Alfred
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nat Immunol. 2002 Jun;3(6):564-9. doi: 10.1038/ni800. Epub 2002 May 20.
Clonotypic T cell receptor (TCR) genes undergo ordered rearrangement and expression in the thymus with the result that TCRalpha and TCRgamma proteins are not expressed in the same cell at the same time. Such "TCRalpha/gamma exclusion" is a feature of normal thymocyte differentiation, but it is abrogated in TCR-transgenic mice, which prematurely express transgenic TCRalpha proteins in early double-negative (DN) thymocytes. We report here that early expression of TCRalpha proteins results in the formation of TCRalphagamma complexes that efficiently signal the differentiation of DN into double-positive thymocytes independently of pre-TCR and TCRbeta expression. Thus, abrogation of TCRalpha/gamma exclusion by early TCRalpha expression results in the formation of isotypically mixed TCRalphagamma complexes whose in vivo signals circumvent TCRbeta selection and redirect thymocyte development along an aberrant developmental pathway.
克隆型T细胞受体（TCR）基因在胸腺中经历有序重排和表达，结果是TCRα和TCRγ蛋白不会在同一细胞中同时表达。这种“TCRα/γ排斥”是正常胸腺细胞分化的一个特征，但在TCR转基因小鼠中被消除，这些小鼠在早期双阴性（DN）胸腺细胞中过早表达转基因TCRα蛋白。我们在此报告，TCRα蛋白的早期表达导致TCRαγ复合物的形成，该复合物能有效地发出信号，使DN分化为双阳性胸腺细胞，而与前TCR和TCRβ表达无关。因此，早期TCRα表达导致的TCRα/γ排斥的消除，导致形成同型混合的TCRαγ复合物，其体内信号绕过TCRβ选择，并使胸腺细胞发育沿着异常的发育途径重新定向。
