Scotet Emmanuel, Martinez Laurent O, Grant Ethan, Barbaras Ronald, Jenö Paul, Guiraud Martine, Monsarrat Bernard, Saulquin Xavier, Maillet Sophie, Estève Jean-Pierre, Lopez Frédéric, Perret Bertrand, Collet Xavier, Bonneville Marc, Champagne Eric
Inserm U601, Institut de Biologie, 9 quai Moncousu, F-44035 Nantes Cedex 01, France.
Immunity. 2005 Jan;22(1):71-80. doi: 10.1016/j.immuni.2004.11.012.
Vgamma9Vdelta2 T lymphocytes, a major gammadelta T lymphocyte subset in humans, display cytolytic activity against various tumor cells upon recognition of yet uncharacterized structures. Here, we show that an entity related to the mitochondrial F1-ATPase is expressed on tumor cell surface and promotes tumor recognition by Vgamma9Vdelta2 T cells. When immobilized, purified F1-ATPase induces selective activation of this lymphocyte subset. The Vgamma9Vdelta2 T cell receptors (TCR) and the F1-ATPase also bind a delipidated form of apolipoprotein A-I (apo A-I), as demonstrated by surface plasmon resonance. Moreover, the presence of apo A-I in the culture medium is required for optimal activation of Vgamma9Vdelta2 T cells by tumors expressing F1-ATPase. This study thus describes an unanticipated tumor recognition mechanism by Vgamma9Vdelta2 lymphocytes and a possible link between gammadelta T cell immunity and lipid metabolism.
Vγ9Vδ2 T淋巴细胞是人类主要的γδ T淋巴细胞亚群，在识别尚未明确的结构后，对多种肿瘤细胞表现出细胞溶解活性。在此，我们表明一种与线粒体F1 - ATP酶相关的实体在肿瘤细胞表面表达，并促进Vγ9Vδ2 T细胞对肿瘤的识别。纯化的F1 - ATP酶固定后可诱导该淋巴细胞亚群的选择性激活。表面等离子体共振显示，Vγ9Vδ2 T细胞受体（TCR）和F1 - ATP酶也能结合脱脂形式的载脂蛋白A - I（apo A - I）。此外，对于表达F1 - ATP酶的肿瘤，培养基中apo A - I的存在是Vγ9Vδ2 T细胞最佳激活所必需的。因此，本研究描述了Vγ9Vδ2淋巴细胞一种意想不到的肿瘤识别机制，以及γδ T细胞免疫与脂质代谢之间可能的联系。
