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Control of T cell antigen reactivity via programmed TCR downregulation

机译:通过程序控制的TCR下调控制T细胞抗原反应性

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The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity. Thus, programmed downregulation of TCR expression represents a negative feedback mechanism for constraining T cell effector function with a suitable time delay to thereby allow pathogen control while avoiding excess inflammatory damage.
机译:T细胞抗原受体(TCR)的独特之处在于,它与配体的亲和力在接触之前是未知的,并且可以相差一个数量级。免疫系统如何调节对抗原表现出截然不同反应性的单个T细胞尚不清楚。在这里,我们发现在克隆扩增的高峰期,活化的CD4(+)T细胞与初始抗原识别的强度成比例地持续下调其TCR表达。该程序性反应以克隆特异性的方式提高了细胞因子产生的阈值并恢复了增殖,并最终排除了具有最高抗原反应性的克隆。因此,TCR表达的程序性下调代表了负反馈机制,该负反馈机制用于在适当的时间延迟内限制T细胞效应子功能,从而允许病原体控制,同时避免过度的炎症损害。

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