Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Nat Immunol. 2012 May 6;13(6):560-8. doi: 10.1038/ni.2301.
Signaling via the T cell antigen receptor (TCR) during the CD4(+)CD8(+) double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell-expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1(-/-) mice had fewer mature thymic CD4(+) and CD8(+) T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-γ1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca(2+)-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.
T 细胞抗原受体 (TCR) 在 CD4(+)CD8(+) 双阳性发育阶段的信号传递决定了胸腺细胞的选择和谱系决定。在这里，我们描述了一种以前未被表征的 T 细胞表达蛋白，Tespa1，它在胸腺细胞的阳性选择过程中具有关键功能。Tespa1(-/-) 小鼠的成熟胸腺 CD4(+)和 CD8(+) T 细胞较少，这反映了胸腺细胞发育受损。Tespa1 与 TCR 信号成分 PLC-γ1 和 Grb2 相关，Tespa1 缺失导致 TCR 信号减弱，反映在 Erk-AP-1 和 Ca(2+)-NFAT 途径的激活缺陷。我们的研究结果表明，Tespa1 是 TCR 信号小体的一个组成部分，通过调节 T 细胞发育过程中的 TCR 信号，对 T 细胞的选择和成熟至关重要。
