细胞毒性T淋巴细胞相关蛋白4（CTLA-4）通过缩短T细胞/抗原呈递细胞（APC）的驻留时间和减少钙动员来破坏ζ链相关蛋白激酶70（ZAP70）微簇的形成。
CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization.
作者信息
Schneider Helga, Smith Xin, Liu Hebin, Bismuth Georges, Rudd Christopher E
机构信息
Cell Signalling Section, Department of Pathology, University of Cambridge, Cambridge, UK.
出版信息
Eur J Immunol. 2008 Jan;38(1):40-7. doi: 10.1002/eji.200737423.
Abstract
CTLA-4 is a co-receptor that modulates the threshold of T cell activation and autoimmunity. We previously showed that CTLA-4 reverses the TCR-mediated stop signal needed for T cell/APC interactions [Schneider et al., Science 2006, 313: 1972]. In this study, using a different T cell system, we show that CTLA-4 expression changed the behavior of T8.1 T cells by reducing the contact time between T cell and APC, preventing re-inforced contacts, and reducing the contact area at the immunological synapse. This led to a major reduction in Ca(2+) influx/mobilization and interleukin-2 production. Further, anti-CD3/CTLA-4 increased T cell motility on antibody-coated glass slides, concurrent with an abrogation of ZAP70 microcluster formation. Our findings further support a role for CTLA-4 in limiting the interaction between T cell and APC that is needed for optimal activation.
摘要
细胞毒性T淋巴细胞相关抗原4（CTLA-4）是一种共受体，可调节T细胞活化阈值和自身免疫。我们之前的研究表明，CTLA-4可逆转T细胞/抗原呈递细胞（APC）相互作用所需的T细胞受体（TCR）介导的停止信号[施奈德等人，《科学》，2006年，第313卷：1972页]。在本研究中，我们使用不同的T细胞系统，发现CTLA-4的表达通过减少T细胞与APC之间的接触时间、防止加强接触以及减小免疫突触处的接触面积，改变了T8.1 T细胞的行为。这导致钙离子（Ca2+）内流/动员以及白细胞介素-2生成大幅减少。此外，抗CD3/CTLA-4增加了T细胞在抗体包被载玻片上的运动能力，同时消除了ζ链相关蛋白激酶70（ZAP70）微簇的形成。我们的研究结果进一步支持了CTLA-4在限制T细胞与APC之间为实现最佳活化所需相互作用方面的作用。
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