CD28
T细胞受体
细胞生物学
信号转导
Jurkat细胞
化学
生物
T细胞
细胞信号
生物物理学
生物化学
免疫系统
免疫学
作者
Wei Yang,Weiling Pan,Shuokai Chen,Nicola Trendel,Shutan Jiang,Feng Xiao,Manman Xue,Wei Wu,Zeli Peng,Xiaoxi Li,Hongbin Ji,Xiaolong Liu,Hai Jiang,Haopeng Wang,Hong‐Bin Shen,Omer Dushek,Hua Li,Chenqi Xu
摘要
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.
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