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

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

来源：eLife, 2016, 5: e10134.

DOI：10.7554/eLife.10134

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.

• 出版日期2016-7-4