Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells
Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells
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DOI：
10.1126/science.aay5516
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发表时间：
2020-02-07
期刊：
影响因子：
56.9
通讯作者：
Uldrich, Adam P.
中科院分区：
文献类型：
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作者：
Rigau, Marc;Ostrouska, Simone;Uldrich, Adam P.
伽马三角洲(Gamma Delta)T细胞对保护性免疫是必不可少的。在人类中，大多数Gamma Delta T细胞表达V Gamma 9V Delta 2(+)T细胞受体(TCR)，该受体对由细胞病原体产生的磷酸抗原(PAG)产生反应，并在癌症中过度表达。然而，这些伽马增量TCR识别的分子靶点是未知的。在这里，我们确定丁亲素2A1(BTN2A1)是与V-Gamma 9(+)TCR伽马链结合的关键配体。BTN2A1与另一种酪亲素BTN3A1结合，它们共同作用启动对PAg的反应。此外，还需要将第二个配体(可能是BTN3A1)与含有V增量2的单独TCR结构域结合。这种独特的依赖于Ag的T细胞激活模式促进了我们对涉及PAg识别的疾病的理解，并为基于Gamma Delta T细胞的免疫疗法的发展创造了机会。
Gamma delta (gamma delta) T cells are essential to protective immunity. In humans, most gamma delta T cells express V gamma 9V delta 2(+) T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these gamma delta TCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the V gamma 9(+) TCR gamma chain. BTN2A1 associates with another butyrophilin, BTN3A1, and these act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating V delta 2 is also required. This distinctive mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of gamma delta T cell-based immunotherapies.