Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength
Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength
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DOI：
10.1016/s1074-7613(01)00259-x
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发表时间：
2002-01-01
期刊：
影响因子：
32.4
通讯作者：
Allison, JP
中科院分区：
文献类型：
--
作者：
Egen, JG;Allison, JP
CD28和CTLA-4与apc表达的B7结合产生T细胞活化的关键调控信号。CD28在T细胞表面表达并增强T细胞扩增，而CTLA-4主要定位于细胞内腔室并抑制T细胞增殖。我们证明CTLA-4具有几种独特的运输特性，可以调节其减弱T细胞反应的能力。重要的是，CTLA-4在免疫突触的积累与TCR信号的强度成正比，这表明接受更强刺激的细胞更容易受到CTLA-4介导的抑制。这可能代表了一种新的反馈控制机制，其中刺激信号调节抑制受体在细胞表面功能相关部位的招募。
CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical regulatory signals for T cell activation. CD28 is expressed on the T cell surface and enhances T cell expansion, while CTLA-4 localizes primarily to an intracellular compartment and inhibits T cell proliferation. We demonstrate that CTLA-4 has several unique trafficking properties that may regulate its ability to attenuate a T cell response. Importantly, accumulation of CTLA-4 at the immunological synapse is proportional to the strength of the TCR signal, suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4-mediated inhibition. This may represent a novel feedback control mechanism in which a stimulatory signal regulates the recruitment of an inhibitory receptor to a functionally relevant site on the cell surface.