The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vγ9Vδ2 T cells.
The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vγ9Vδ2 T cells.
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DOI：
10.1016/j.immuni.2014.03.003
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发表时间：
2014-04-17
期刊：
影响因子：
32.4
通讯作者：
Adams, Erin J.
中科院分区：
文献类型：
--
作者：
Sandstrom, Andrew;Peigne, Cassie-Marie;Leger, Alexandra;Crooks, James E.;Konczak, Fabienne;Gesnel, Marie-Claude;Breathnach, Richard;Bonneville, Marc;Scotet, Emmanuel;Adams, Erin J.
在人类中，Vγ9Vδ2 T细胞通过识别含有磷酸抗原（pAgs）的小焦磷酸盐来检测肿瘤细胞和包括结核分枝杆菌在内的微生物感染。pAg介导的v - γ - 9v δ2 T细胞活化的关键是butyrophilin 3A1 （BTN3A1）蛋白，该蛋白含有对pAg反应性至关重要的细胞内B30.2结构域。在这里，我们通过结构、生物物理和功能方法证明了BTN3A1的胞内B30.2结构域通过带正电的表面口袋直接结合pAg。口袋残基的电荷反转消除了结合和v - γ - 9v - δ2 T细胞活化。我们还在该口袋中发现了一个功能获得突变，当将其引入非刺激性BTN3A3异构体的B30.2结构域时，会转移pAg结合能力和Vγ9Vδ2 T细胞活化。这些研究表明，BTN3A1分子对pAg代谢物浓度变化的内部感知是v γ - 9v - δ2 T细胞检测感染和肿瘤发生的关键步骤。
In humans, Vγ9Vδ2 T cells detect tumor cells and microbial infections including Mycobacterium tuberculosis through recognition of small pyrophosphate containing organic molecules known as phosphoantigens (pAgs). Key to pAg-mediated activation of Vγ9Vδ2 T cells is the butyrophilin 3A1 (BTN3A1) protein that contains an intracellular B30.2 domain critical to pAg reactivity. Here, we have demonstrated through structural, biophysical and functional approaches that the intracellular B30.2 domain of BTN3A1 directly binds pAg through a positively-charged surface pocket. Charge-reversal of pocket residues abrogates binding and Vγ9Vδ2 T cell activation. We have also identified a gain-of-function mutation within this pocket that when introduced into B30.2 domain of the non-stimulatory BTN3A3 isoform, transfers pAg binding ability and Vγ9Vδ2 T cell activation. These studies demonstrate that internal sensing of changes in pAg metabolite concentrations by BTN3A1 molecules is a critical step in Vγ9Vδ2 T cell detection of infection and tumorigenesis.
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DOI：
10.1107/s0907444909017855
发表时间：
2009-08-01
影响因子：
2.2
作者：
Andersen, Ole Andreas;Schoenfeld, Dorian Leo;Barker, John
通讯作者：
Barker, John
影响因子：
4.8
作者：
Espinosa, E;Belmant, C;Fournié, JJ
通讯作者：
Fournié, JJ
影响因子：
1.8
作者：
Julian, RR;Beauchamp, JL
通讯作者：
Beauchamp, JL
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
4.4
作者：
Rhodes, DA;Stammers, M;Trowsdale, J
通讯作者：
Trowsdale, J