Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, U563, France.
J Immunol. 2010 Jun 15;184(12):6920-8. doi: 10.4049/jimmunol.0904024. Epub 2010 May 7.
Human Vgamma9Vdelta2 T lymphocytes are activated by phosphoantigens provided exogenously or produced by tumors and infected cells. Activation requires a contact between Vgamma9Vdelta2 cells and neighboring cells. We previously reported a role for cell surface F1-adenosine triphosphatase (ATPase) in T cell activation by tumors and specific interactions between Vgamma9Vdelta2 TCRs and purified F1-ATPase. 721.221 cells do not express surface F1-ATPase and do not support phosphoantigen responses unless they are rendered apoptotic by high doses of zoledronate, a treatment that promotes F1-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 F1-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 F1-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 F1-ATPase. In the absence of Vgamma9Vdelta2 cells, triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester immobilized on F1-ATPase is protected from nucleotide pyrophosphatase activity, as is the antigenic activity of stimulatory target cells. Our experiments support the notion that Vgamma9Vdelta2 T cells are dedicated to the recognition of phosphoantigens on cell membranes in the form of nucleotide derivatives that can bind to F1-ATPase acting as a presentation molecule.
人 Vγ9Vδ2 T 淋巴细胞可被外来提供的磷酸化抗原或肿瘤和感染细胞产生的磷酸化抗原激活。激活需要 Vγ9Vδ2 细胞与邻近细胞之间的接触。我们之前报道了在肿瘤和特异性 Vγ9Vδ2 TCR 与纯化的 F1-ATP 酶之间的相互作用中，细胞表面 F1-三磷酸腺苷酶（ATP 酶）在 T 细胞激活中的作用。721.221 细胞不表达表面 F1-ATP 酶，除非用高剂量唑来膦酸盐处理使其凋亡，否则不能支持磷酸化抗原反应，这种处理方法促进 F1 的表达和内源性磷酸化抗原的产生。通过监测单细胞中的钙流，我们在这项研究中表明，T 细胞与聚苯乙烯珠上的 F1-ATP 酶接触可以部分替代磷酸化抗原反应过程中的细胞间接触刺激。三磷酸腺苷 1-腺嘌呤-5′-基酯 3-(3-甲基丁-3-烯基)酯，是异戊烯焦磷酸的腺嘌呤衍生物，可稳定结合到 F1-ATP 酶包被的珠上，并促进 TCR 聚集、淋巴因子分泌和细胞溶解过程的激活，只要核苷酸焦磷酸酶活性存在。它还作为 F1-ATP 酶的变构激活剂。在没有 Vγ9Vδ2 细胞的情况下，固定在 F1-ATP 酶上的三磷酸腺苷 1-腺嘌呤-5′-基酯 3-(3-甲基丁-3-烯基)酯，以及刺激靶细胞的抗原活性，都免受核苷酸焦磷酸酶活性的影响。我们的实验支持了这样一种观点，即 Vγ9Vδ2 T 细胞专门识别细胞膜上的磷酸化抗原，其形式为可与作为呈递分子的 F1-ATP 酶结合的核苷酸衍生物。
