Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Eur J Immunol. 2014 Sep;44(9):2571-6. doi: 10.1002/eji.201444712. Epub 2014 Jun 30.
Pyrophosphorylated metabolites of isoprenoid-biosynthesis (phosphoantigens, PAgs) activate Vγ9Vδ2 T cells during infections and trigger antitumor activity. This activation depends on expression of butyrophilin 3 A1 (BTN3A1) by antigen-presenting cells. This report defines the minimal genetic requirements for activation of Vγ9Vδ2 T cells by PAgs and mAb 20.1. We compared PAg-presentation by BTN3A1-transduced CHO hamster cells with that of CHO cells containing the complete human chromosome 6 (Chr6). BTN3A1 expression alone was sufficient for activation of Vγ9Vδ2 T-cell receptor transductants by mAb 20.1., while activation by PAgs also required the presence of Chr6. We take this finding as evidence that gene(s) on Chr6 in addition to BTN3A1 are mandatory for PAg-mediated activation of Vγ9Vδ2 T cells. This observation is important for the design of animal models for PAg-mediated immune responses and provokes speculations about the analogy between genes controlling PAg presentation and MHC-localized genes controlling peptide-antigen presentation.
异戊烯基生物合成的焦磷酸化代谢物（磷酸抗原，PAgs）在感染期间激活 Vγ9Vδ2 T 细胞，并触发抗肿瘤活性。这种激活依赖于抗原呈递细胞表达丁酰膦蛋白 3A1（BTN3A1）。本报告定义了 PAgs 和 mAb 20.1 激活 Vγ9Vδ2 T 细胞的最小遗传要求。我们比较了 BTN3A1 转导的 CHO 仓鼠细胞与含有完整人类染色体 6（Chr6）的 CHO 细胞中 PAgs 的呈现。BTN3A1 表达本身足以激活 mAb 20.1 的 Vγ9Vδ2 T 细胞受体转染子，而 PAgs 的激活还需要 Chr6 的存在。我们将这一发现视为 Chr6 上除 BTN3A1 之外的基因对于 PAgs 介导的 Vγ9Vδ2 T 细胞激活是必需的证据。这一观察结果对于设计 PAgs 介导的免疫反应的动物模型很重要，并引发了关于控制 PAgs 呈现的基因与控制肽抗原呈现的 MHC 定位基因之间类比的推测。
