B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator
B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator
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DOI：
10.1038/ni1144
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发表时间：
2005-01-01
影响因子：
30.5
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Sedy, JR;Gavrieli, M;Murphy, KM
B和T淋巴细胞衰减剂（BTLA）向B和T细胞提供抑制信号。以前，间接观察表明B7 x是BTLA的配体。在这里，我们表明BTLA不结合B7 x，相反，我们确定疱疹病毒进入介质（HVEM）作为独特的BTLA配体。BTLA结合HVEM的最远膜的富含半胱氨酸的结构域，不同于配体LIGHT和α-光敏素结合HVEM的区域。HVEM诱导BTLA酪氨酸磷酸化和酪氨酸磷酸酶SHP-2的缔合，并抑制抗原驱动的T细胞增殖，提供了向非肿瘤坏死因子家族配体反向信号传导的实例。小鼠和人之间BTLA-HVEM相互作用的保守性表明该系统是调节免疫应答中淋巴细胞活化和/或稳态的重要途径。
B and T lymphocyte attenuator (BTLA) provides an inhibitory signal to B and T cells. Previously, indirect observations suggested that B7x was a ligand for BTLA. Here we show that BTLA does not bind B7x; instead, we identify herpesvirus entry mediator (HVEM) as the unique BTLA ligand. BTLA bound the most membrane-distal cysteine-rich domain of HVEM, distinct from regions where the ligands LIGHT and lymphotoxin-alpha bound HVEM. HVEM induced BTLA tyrosine phosphorylation and association of the tyrosine phosphatase SHP-2 and repressed antigen-driven T cell proliferation, providing an example of reverse signaling to a non-tumor necrosis factor family ligand. The conservation of the BTLA-HVEM interaction between mouse and human suggests that this system is an important pathway regulating lymphocyte activation and/or homeostasis in the immune response.