CD80 和 CD86 的跨胞吞作用：CTLA-4 细胞外功能的分子基础。
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
机构信息
Medical Research Council (MRC) Centre for Immune Regulation, School of Immunity and Infection, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, UK.
出版信息
Science. 2011 Apr 29;332(6029):600-3. doi: 10.1126/science.1202947. Epub 2011 Apr 7.
Abstract
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.
摘要
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）是 T 细胞免疫反应的一个必要的负调控因子，其作用机制仍存在争议。CTLA-4 与其共刺激受体 CD28 共享两个配体（CD80 和 CD86）。在这里，我们证明 CTLA-4 可以通过跨内吞作用从相反的细胞中捕获其配体。配体被去除后，这些共刺激配体在表达 CTLA-4 的细胞内被降解，导致通过 CD28 的共刺激受损。T 细胞受体的结合刺激了从抗原呈递细胞中获得 CD86，并在体外和体内观察到。这些数据揭示了一种免疫调节机制，其中 CTLA-4 作为效应分子，通过细胞外配体的耗竭来抑制 CD28 的共刺激，这解释了 CD28-CTLA-4 系统的许多已知特征。
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