F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells
F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells
复制标题
DOI：
10.4049/jimmunol.0904024
复制
发表时间：
2010-06-15
影响因子：
4.4
通讯作者：
Champagne, Eric
中科院分区：
文献类型：
--
作者：
Mookerjee-Basu, Jayati;Vantourout, Pierre;Champagne, Eric
人 V γ 9V δ 2 T 淋巴细胞被外源提供的或由肿瘤和感染细胞产生的磷酸抗原激活。激活需要 V gamma 9V delta 2 电池与相邻电池之间的接触。我们之前报道了细胞表面 F-1-三磷酸腺苷酶 (ATPase) 在肿瘤 T 细胞激活中的作用以及 V gamma 9V delta 2 TCR 和纯化的 F-1-ATPase 之间的特异性相互作用。 721.221 细胞不表达表面 F-1-ATP 酶，也不支持磷酸抗原反应，除非用高剂量的唑来膦酸盐（一种促进 F-1 表达以及内源性磷酸抗原产生的治疗方法）使其凋亡。通过监测单细胞中的钙通量，我们在这项研究中表明，T 细胞与聚苯乙烯珠上的 F-1-ATP 酶的接触可以部分替代磷酸抗原反应期间的细胞与细胞接触刺激。三磷酸 1-腺苷-5'-基酯 3-(3-甲基丁-3-烯基)酯是异戊烯基焦磷酸的腺苷酸化衍生物，可以稳定地与 F-1-ATPase 包被的珠子结合，并促进 TCR 聚集、淋巴因子分泌和细胞溶解过程的激活，前提是存在核苷酸焦磷酸酶活性。它还充当 F-1-ATP 酶的变构激活剂。在缺乏 V gamma 9V delta 2 细胞的情况下，固定在 F-1-ATPase 上的三磷酸 1-腺苷-5'-基酯 3-(3-methylbut-3-enyl) 酯受到保护，免受核苷酸焦磷酸酶活性的影响，刺激性靶细胞的抗原活性也是如此。我们的实验支持这样的观点，即 V gamma 9V delta 2 T 细胞致力于识别细胞膜上核苷酸衍生物形式的磷酸抗原，这些核苷酸衍生物可以与作为呈递分子的 F-1-ATPase 结合。免疫学杂志，2010，184：6920-6928。
Human V gamma 9V delta 2 T lymphocytes are activated by phosphoantigens provided exogenously or produced by tumors and infected cells. Activation requires a contact between V gamma 9V delta 2 cells and neighboring cells. We previously reported a role for cell surface F-1-adenosine triphosphatase (ATPase) in T cell activation by tumors and specific interactions between V gamma 9V delta 2 TCRs and purified F-1-ATPase. 721.221 cells do not express surface F-1-ATPase and do not support phosphoantigen responses unless they are rendered apoptotic by high doses of zoledronate, a treatment that promotes F-1-expression as well as endogenous phosphoantigen production. By monitoring calcium flux in single cells, we show in this study that contact of T cells with F-1-ATPase on polystyrene beads can partially replace the cell-cell contact stimulus during phosphoantigen responses. Triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester, an adenylated derivative of isopentenyl pyrophosphate, can stably bind to F-1-ATPase-coated beads and promotes TCR aggregation, lymphokine secretion, and activation of the cytolytic process provided that nucleotide pyrophosphatase activity is present. It also acts as an allosteric activator of F-1-ATPase. In the absence of V gamma 9V delta 2 cells, triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester immobilized on F-1-ATPase is protected from nucleotide pyrophosphatase activity, as is the antigenic activity of stimulatory target cells. Our experiments support the notion that V gamma 9V delta 2 T cells are dedicated to the recognition of phosphoantigens on cell membranes in the form of nucleotide derivatives that can bind to F-1-ATPase acting as a presentation molecule. The Journal of Immunology, 2010, 184: 6920-6928.