Control of T cell antigen reactivity via programmed TCR downregulation.
Control of T cell antigen reactivity via programmed TCR downregulation.
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DOI：
10.1038/ni.3386
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发表时间：
2016-04
影响因子：
30.5
通讯作者：
van Heijst JW
中科院分区：
文献类型：
--
作者：
Gallegos AM;Xiong H;Leiner IM;Sušac B;Glickman MS;Pamer EG;van Heijst JW
T细胞受体（TCR）是独特的，因为其对配体的亲和力在遇到之前是未知的，并且可以按数量级变化。免疫系统如何调节对抗原表现出高度不同反应性的单个T细胞仍不清楚。在这里，我们发现，活化的CD4+ T细胞，在克隆扩增的高峰，持续下调TCR表达的强度成比例的初始抗原识别。这种程序化反应以克隆特异性方式增加细胞因子产生和回忆增殖的阈值，最终排除具有最高抗原反应性的克隆。因此，程序性TCR下调代表负反馈机制，以适当的时间延迟限制T细胞效应子功能，从而允许病原体控制，同时避免过度的炎性损伤。
The T cell receptor (TCR) is unique in that its affinity for ligand is unknown prior to encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display highly different reactivity to antigen remains unclear. Here we identified that activated CD4+ T cells, at the peak of clonal expansion, persistently downregulate TCR expression in proportion to the strength of initial antigen recognition. This programmed response increases the threshold for cytokine production and recall proliferation in a clone-specific manner, ultimately excluding clones with the highest antigen reactivities. Thus, programmed TCR downregulation represents a negative feedback mechanism to constrain T cell effector function with a suitable time delay, thereby allowing pathogen control while avoiding excess inflammatory damage.