Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells

TCR 结合的亲和力和剂量与 CD4+ T 细胞中增强子和基因活性成正比

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作者:Karmel A Allison ,Eniko Sajti ,Jana G Collier ,David Gosselin ,Ty Dale Troutman ,Erica L Stone ,Stephen M Hedrick ,Christopher K Glass

Abstract

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.

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