Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+T cells
Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+T cells
复制标题
DOI：
10.7554/elife.10134
复制
发表时间：
2016-07-04
期刊：
影响因子：
7.7
通讯作者：
Glass, Christopher K.
中科院分区：
文献类型：
--
作者：
Allison, Karmel A.;Sajti, Eniko;Glass, Christopher K.
T细胞受体（TCR）与抗原相互作用的亲和力和剂量决定了CD 4 + T细胞应答的大小，但关于TCR接合到下游信号的定量翻译仍存在问题。我们发现，虽然小鼠CD 4 + T细胞抗原刺激的反应是双峰，激活的细胞表现出类似的信号强度成正比的反应。基因表达输出反映TCR信号强度，提供T细胞活化的特征。表达变化依赖于预先建立的增强子景观和AP-1结合位点的定量乙酰化。最后，我们表明，激活基因的分级表达依赖于ERK通路的激活，这表明ERK-AP-1轴在翻译TCR信号强度成比例激活增强子和T细胞功能所必需的基因中起着重要作用。
Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function.