The balance between T cell receptor signaling and degradation at the center of the immunological synapse is determined by antigen quality
The balance between T cell receptor signaling and degradation at the center of the immunological synapse is determined by antigen quality
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DOI：
10.1016/j.immuni.2008.06.014
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发表时间：
2008-09-19
期刊：
影响因子：
32.4
通讯作者：
Shaw, Andrey S.
中科院分区：
文献类型：
--
作者：
Cemerski, Saso;Das, Jayajit;Shaw, Andrey S.
免疫突触中心（中央超分子激活簇或cSMAC）的作用是有争议的。一个模型表明cSMAC的作用取决于抗原质量，并且可以增强信号传导和受体下调，而第二个模型提出cSMAC的唯一功能是下调信号传导。模型之间的一个重要区别是信号是否发生在cSMAC中。在这里，我们证明了在早期的时间点，信号发生在cSMAC之外，但在稍后的时间点发生在cSMAC中。此外，我们表明cSMAC形成增强了TCR弱激动剂的刺激效力。结合以前的研究表明，cSMAC形成减少信号的强激动剂，我们的数据支持一个模型，提出信号和受体降解都发生在cSMAC和信号之间的平衡和退化的突触是由抗原的质量。
The role of the center of the immunological synapse (the central supramolecular activation cluster or cSMAC) is controversial. One model suggests that the role of the cSMAC depends on antigen quality and can both enhance signaling and receptor downregulation, whereas a second model proposes that the sole function of the cSMAC is to downregulate signaling. An important distinction between the models is whether signaling occurs in the cSMAC. Here, we demonstrate that at early time points, signaling occurs outside the cSMAC, but occurs in the cSMAC at later time points. Additionally, we show that cSMAC formation enhances the stimulatory potency of weak agonists for the TCR. Combined with previous studies showing that cSMAC formation decreases the signaling by strong agonists, our data support a model proposing that signaling and receptor degradation both occur in the cSMAC and that the balance between signaling and degradation in the synapse is determined by antigen quality.