Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing
Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing
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DOI：
10.1002/eji.202350700
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发表时间：
2023-12-07
影响因子：
5.4
通讯作者：
Turner，Martin
中科院分区：
文献类型：
--
作者：
Petkau，Georg;Mitchell，Twm J.;Turner，Martin
单个T细胞如何在分子水平上竞争IL-2并对IL-2做出反应，因此，这如何影响群体动态和高亲和力克隆的选择仍然知之甚少。在这里，我们描述了RNA结合蛋白ZFP 36 L1如何作为TCR亲和力的传感器来促进高亲和力CD 8 T细胞的克隆扩增。作为一个不连贯的前馈回路的一部分，ZFP 36 L1在抑制细胞因子信号传导的多种负调节因子和介导基于IL-2竞争的选择机制方面具有非冗余作用。我们认为，ZFP 36 L1作为抗原亲和力的传感器，并通过对IL-2的分级反应建立高亲和力T细胞的优势。
How individual T cells compete for and respond to IL‐2 at the molecular level, and, as a consequence, how this shapes population dynamics and the selection of high‐affinity clones is still poorly understood. Here we describe how the RNA binding protein ZFP36L1, acts as a sensor of TCR affinity to promote clonal expansion of high‐affinity CD8 T cells. As part of an incoherent feed‐forward loop, ZFP36L1 has a nonredundant role in suppressing multiple negative regulators of cytokine signaling and mediating a selection mechanism based on competition for IL‐2. We suggest that ZFP36L1 acts as a sensor of antigen affinity and establishes the dominance of high‐affinity T cells by installing a hierarchical response to IL‐2.