Nakayama K, Loh D Y
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Science. 1992 Jul 3;257(5066):94-6. doi: 10.1126/science.1621101.
Activation of protein-tyrosine kinases (PTKs) is required for signal transduction during T cell activation, although the pathway used during thymic selection is unknown. An in vitro system was established in which T cell receptor transgenic thymocytes underwent clonal deletion in response to peptide antigen. The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined. Clonal deletion occurred while T cell activation was inhibited and when no p56lck activity was evident. Thus, p56lck is not required for the antigen-stimulated step of clonal deletion of immature thymocytes, and negative selection proceeds via a distinct pathway.
T细胞活化过程中的信号转导需要蛋白酪氨酸激酶（PTK）的激活，尽管胸腺选择过程中所使用的信号通路尚不清楚。我们建立了一个体外系统，其中T细胞受体转基因胸腺细胞会对肽抗原产生反应而发生克隆性缺失。研究了两种PTK特异性抑制剂，即除莠霉素A和染料木黄酮，对未成熟胸腺细胞克隆性缺失以及成熟胸腺细胞活化的影响。在T细胞活化受到抑制且无明显p56lck活性时，仍会发生克隆性缺失。因此，未成熟胸腺细胞克隆性缺失的抗原刺激步骤并不需要p56lck，阴性选择通过一条不同的信号通路进行。
