Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation
Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation
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DOI：
10.4049/jimmunol.172.6.3662
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Vignali, DAA
中科院分区：
文献类型：
--
作者：
La Gruta, NL;Liu, HY;Vignali, DAA
T 细胞激活的一个标志是连接诱导的 TCR:CD3 复合物下调。然而，人们对驱动这一过程的分子事件知之甚少。 CD3 zeta 链已被证明在调节 TCR:CD3 复合物的组装、运输和细胞表面表达方面发挥着独特的作用。在这项研究中，我们研究了 MHC: 肽复合物连接后 CD3 和 TCRalphabetaCD3epsilondeltagamma 复合物之间的关系。我们的结果表明，T 细胞刺激后，与 TCR:CD3 复合物无关的游离表面 CD3zeta 显着增加。这可能反映了 CD3zeta 从 TCRalphabetaCD3epsilondeltagamma 复合物解离或细胞内 CD3 直接转运至细胞表面。我们还表明，MHC：肽连接也会导致 TCR 相关的 CD3zeta NH2 末端暴露，该末端通常埋藏在复合物中。这些观察结果似乎依赖于 Src 家族蛋白酪氨酸激酶，众所周知，Src 家族蛋白酪氨酸激酶对于 T 细胞的有效激活至关重要。这些数据表明了一种机制，通过该机制可以将连接的 TCR 与未连接的 TCR 区分开并选择性下调。
A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 zeta-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3 and the TCRalphabetaCD3epsilondeltagamma complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3zeta which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3zeta from the TCRalphabetaCD3epsilondeltagamma complex or transport of intracellular CD3 directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3zeta NH2 terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src family protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.