期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 24, 期 12, 页码 1081-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3489
关键词
-
资金
- NSFC [31370860, 31425009, 31530022, 31621003, 31470734, 31670751]
- CAS [XDB08020100]
- MOST [2014CB541903]
- Wellcome Trust
- Royal Society [098363]
- Systems Biology DTC by the Engineering and Physical Science Research Council (UK)
- Engineering and Physical Sciences Research Council [1512113] Funding Source: researchfish
CD28 provides an essential costimulatory signal for T cell activation, and its function is critical in antitumor immunity. However, the molecular mechanism of CD28 transmembrane signaling remains elusive. Here we show that the conformation and signaling of CD28 are regulated by two counteractive charged factors, acidic phospholipids and Ca2+ ions. NMR spectroscopy analyses showed that acidic phospholipids can sequester CD28 signaling motifs within the membrane, thereby limiting CD28 basal signaling. T cell receptor (TCR) activation induced an increase in the local Ca2+ concentration around CD28, and Ca2+ directly disrupted CD28-lipid interaction, leading to opening and signaling of CD28. We observed that the TCR, Ca2+, and CD28 together form a dual-positive-feedback circuit that substantially amplifies T cell signaling and thus increases antigen sensitivity. This work unravels a new regulatory mechanism for CD28 signaling and thus contributes to the understanding of the dependence of costimulation signaling on TCR signaling and the high sensitivity of T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据