Molecular basis of T cell inactivation by CTLA-4
Molecular basis of T cell inactivation by CTLA-4
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DOI：
10.1126/science.282.5397.2263
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发表时间：
1998-12-18
期刊：
影响因子：
56.9
通讯作者：
Bluestone, JA
中科院分区：
文献类型：
--
作者：
Lee, KM;Chuang, E;Bluestone, JA
CTLA-4是一种T细胞功能的负调节因子，它与原代T细胞中的T细胞受体（TCR）复合物zeta链相结合。在293个转染子中，p56（lck）诱导的酪氨酸磷酸化增强了TCR zeta与CTLA-4的结合。CTLA-4相关酪氨酸磷酸酶SHP-2的共表达导致与CTLA-4结合的TCR zeta的去磷酸化，并消除了p56（lck）诱导的TCR zeta-CTLA-4相互作用。因此，CTLA-4通过结合TCR ζ并在T细胞活化后抑制酪氨酸磷酸化来抑制TCR信号转导。这些发现对T细胞功能和T细胞耐受性的负调节具有广泛的意义。
CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells, The association of TCR zeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)- induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCR zeta bound to CTLA-4 and abolished the p56(lck)-inducible TCR zeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCR zeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.