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

Autor: Karmel A Allison, Eniko Sajti, Jana G Collier, David Gosselin, Ty Dale Troutman, Erica L Stone, Stephen M Hedrick, Christopher K Glass
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: eLife, Vol 5 (2016)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.10134
Popis: 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.
Databáze: Directory of Open Access Journals