Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
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DOI：
10.1126/science.1202947
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发表时间：
2011-04-29
期刊：
影响因子：
--
通讯作者：
Sansom DM
中科院分区：
文献类型：
--
作者：
Qureshi OS;Zheng Y;Nakamura K;Attridge K;Manzotti C;Schmidt EM;Baker J;Jeffery LE;Kaur S;Briggs Z;Hou TZ;Futter CE;Anderson G;Walker LS;Sansom DM
CTLA-4是T细胞免疫应答的重要负性调节因子，其作用机制一直备受争议。CTLA-4还与刺激性受体CD28共享两个配体(CD80和CD86)。在这里，我们展示了CTLA-4可以通过跨内吞过程从对立细胞中捕获其配体。去除后，这些共刺激配体在表达CTLA-4的细胞内降解，导致通过CD28的协同刺激受损。通过TCR结合刺激抗原提呈细胞获得CD86，并在体外和体内观察。这些数据揭示了一种免疫调节机制，即CTLA-4作为效应分子，通过细胞-外在配体的耗尽来抑制CD28的共刺激，这解释了CD28-CTLA-4系统的许多已知特征。
CTLA-4 is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 also 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. Following 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 TCR engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation whereby 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.
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影响因子：
8.7
作者：
Rudd CE;Taylor A;Schneider H
通讯作者：
Schneider H
影响因子：
4.4
作者：
Iida, T;Ohno, H;Saito, T
通讯作者：
Saito, T
影响因子：
32.4
作者：
TIVOL, EA;BORRIELLO, F;SHARPE, AH
通讯作者：
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影响因子：
4.4
作者：
Mead, KI;Zheng, Y;Sansom, DM
通讯作者：
Sansom, DM
DOI：
10.1084/jem.20081811
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Friedline RH;Brown DS;Nguyen H;Kornfeld H;Lee J;Zhang Y;Appleby M;Der SD;Kang J;Chambers CA
通讯作者：
Chambers CA