Peigné Cassie-Marie, Léger Alexandra, Gesnel Marie-Claude, Konczak Fabienne, Olive Daniel, Bonneville Marc, Breathnach Richard, Scotet Emmanuel
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, INSERM, CNRS, Université d'Angers, Université de Nantes, 44035 Nantes, France.
Labex-Immunotherapy Graft Oncology, Nantes 44000, France; and.
J Immunol. 2017 Jun 1;198(11):4228-4234. doi: 10.4049/jimmunol.1601910. Epub 2017 May 1.
Vγ9Vδ2 T lymphocytes are the major human peripheral γδ T cell subset, with broad reactivity against stressed human cells, including tumor cells. Vγ9Vδ2 T cells are specifically activated by small phosphorylated metabolites called phosphoantigens (PAg). Stress-induced changes in target cell PAg levels are specifically detected by butyrophilin (BTN)3A1, using its intracellular B30.2 domain. This leads to the activation of Vγ9Vδ2 T cells. In this study, we show that changes in the juxtamembrane domain of BTN3A1, but not its transmembrane domain, induce a markedly enhanced or reduced γδ T cell reactivity. There is thus a specific requirement for BTN3A1's juxtamembrane domain for correct γδ T cell-related function. This work identified, as being of particular importance, a juxtamembrane domain region of BTN3A molecules identified as a possible dimerization interface and that is located close to the start of the B30.2 domain.
Vγ9Vδ2 T淋巴细胞是人类外周血中主要的γδ T细胞亚群，对包括肿瘤细胞在内的应激人类细胞具有广泛的反应性。Vγ9Vδ2 T细胞被称为磷酸抗抗原（PAg）的小磷酸化代谢产物特异性激活。应激诱导的靶细胞PAg水平变化由嗜乳脂蛋白（BTN）3A1利用其细胞内B30.2结构域特异性检测到。这导致Vγ9Vδ2 T细胞的激活。在本研究中，我们表明，BTN3A1的近膜结构域而非其跨膜结构域的变化会诱导γδ T细胞反应性显著增强或降低。因此，BTN3A1的近膜结构域对于正确的γδ T细胞相关功能具有特定要求。这项工作确定了BTN3分子的一个近膜结构域区域特别重要，该区域被确定为一个可能的二聚化界面，且位于靠近B30.2结构域起始处。
