Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76
Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76
复制标题
DOI：
10.1038/ni1272
复制
发表时间：
2005-12-01
影响因子：
30.5
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Yokosuka, T;Sakata-Sogawa, K;Saito, T
T细胞受体（TCR）的激活和信号传导先于免疫突触的形成，并在突触形成后持续数小时。然而，最初和持续的TCR信号的确切物理位置尚不明确。我们在这里报道，T细胞激活是在初始接触部位和成熟免疫突触外围产生的含tcr微团中启动和维持的。在细胞外围不断产生含有tcr、酪氨酸激酶Zap70和接头分子SLP-76的微团。TCR微团簇向中心超分子团簇迁移，而Zap70和SLP-76在微团簇与富含TCR的中心超分子团簇结合之前就与这些微团簇分离。酪氨酸磷酸化和钙内流诱导微团形成的初始接触点。信号传导的抑制阻止了Zap70进入微团簇。这些结果表明，富含TCR的微团簇启动并维持TCR信号传导。
T cell receptor (TCR) activation and signaling precede immunological synapse formation and are sustained for hours after initiation. However, the precise physical sites of the initial and sustained TCR signaling are not definitively known. We report here that T cell activation was initiated and sustained in TCR-containing microclusters generated at the initial contact sites and the periphery of the mature immunological synapse. Microclusters containing TCRs, the tyrosine kinase Zap70 and the adaptor molecule SLP-76 were continuously generated at the periphery. TCR microclusters migrated toward the central supramolecular cluster, whereas Zap70 and SLP-76 dissociated from these microclusters before the microclusters coalesced with the TCR-rich central supramolecular cluster. Tyrosine phosphorylation and calcium influx were induced as microclusters formed at the initial contact sites. Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling.