PD-1 signaling in primary T cells.
PD-1 signaling in primary T cells.
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DOI：
10.1111/j.1600-065x.2009.00767.x
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发表时间：
2009-05
影响因子：
8.7
通讯作者：
Riley JL
中科院分区：
文献类型：
--
作者：
Riley JL
程序性死亡-1 (PD-1) 是一种调节适应性免疫反应的细胞表面分子。 PD-1 与其配体 PD-L1 或 PD-L2 的结合可转导抑制 T 细胞增殖、细胞因子产生和细胞溶解功能的信号。虽然人们对 PD-1 在调节初级免疫反应和 T 细胞耗竭中发挥的生物学作用有很多了解，但关于 PD-1 连接如何改变信号通路的了解相对较少。 PD-1 连接已知可抑制近膜 T 细胞信号传导事件，而相关抑制分子细胞毒性 T 淋巴细胞抗原 4 的连接似乎可靶向更多下游信号传导通路。深入了解 PD-1 信号转导的一个主要障碍是缺乏研究信号转导的生理模型。本综述重点关注：1) PD-1 连接改变的信号通路，2) PD-1 磷酸化后招募的因子，3) 探索 PD-1 连接在免疫细胞分化的各个阶段诱导不同信号的假设。最后，我们描述了在不存在激动剂抗体的情况下使用原代细胞剖析 PD-1 胞质尾部功能的模型。
Programmed death-1 (PD-1) is a cell surface molecule that regulates the adaptive immune response. Engagement of PD-1 by its ligands PD-L1 or PD-L2 transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function. While a great deal is known concerning the biological roles PD-1 plays in regulating the primary immune response and in T-cell exhaustion, comparatively little is known regarding how PD-1 ligation alters signaling pathways. PD-1 ligation is known to inhibit membrane-proximal T-cell signaling events, while ligation of the related inhibitory molecule cytotoxic T lymphocyte antigen-4 appears to target more downstream signaling pathways. A major obstacle to an in-depth understanding of PD-1 signaling is the lack of physiologic models in which to study signal transduction. This review focuses on: 1) signaling pathways altered by PD-1 ligation, 2) factors recruited upon PD-1 phosphorylation, and 3) exploring the hypothesis that PD-1 ligation induces distinct signals during various stages of immune-cell differentiation. Lastly, we describe models to dissect the function of the PD-1 cytoplasmic tail using primary cells in the absence of agonist antibodies.