Bürk M R, Mori L, De Libero G
Department of Research, University Hospital, Basel, Switzerland.
Eur J Immunol. 1995 Jul;25(7):2052-8. doi: 10.1002/eji.1830250737.
Many different pathogens stimulate cells bearing the V gamma 9-V delta 2 T cell receptor (TCR), which represent the most abundant population of human gamma delta cells. The antigens responsible for the stimulation of these gamma delta cells are not well characterized. Here, we describe six non-peptidic molecules which share this property: isopentenylpyrophosphate, dimethylallylpyrophosphate, 2,3-diphosphoglyceric acid, glycerol-3-phosphoric acid, xylose-1-phosphate, and ribose-1-phosphate. All these molecules are naturally occurring metabolites in prokaryotic and eukaryotic cells, and stimulate freshly isolated gamma delta cells from peripheral blood of different donors as well as established gamma delta clones. Comparison of their structure with that of similar but inactive molecules showed that both the number and position of the phosphate groups, as well as the residues connected with the carbon backbone are required for stimulation. The CD3-TCR complex is involved in cell triggering as shown by inhibition with anti-CD3 Fab fragments. However, all gamma delta clones were broadly cross-reactive and we could not isolate cells specific for only one ligand. The capacity of this frequent subset of gamma delta cells to recognize common bacterial metabolites confers the advantage to react rapidly to different invading pathogens.
许多不同的病原体可刺激带有Vγ9-Vδ2 T细胞受体（TCR）的细胞，这类细胞是人类γδ细胞中数量最多的群体。刺激这些γδ细胞的抗原尚未得到充分表征。在此，我们描述了具有这种特性的六种非肽类分子：异戊烯基焦磷酸、二甲基烯丙基焦磷酸、2,3-二磷酸甘油酸、甘油-3-磷酸、木糖-1-磷酸和核糖-1-磷酸。所有这些分子都是原核细胞和真核细胞中的天然代谢产物，可刺激来自不同供体外周血的新鲜分离的γδ细胞以及已建立的γδ克隆。将它们的结构与类似但无活性的分子结构进行比较表明，刺激需要磷酸基团的数量和位置以及与碳骨架相连的残基。如用抗CD3 Fab片段抑制所示，CD3-TCR复合物参与细胞触发。然而，所有γδ克隆都具有广泛的交叉反应性，我们无法分离出仅对一种配体特异的细胞。γδ细胞的这一常见亚群识别常见细菌代谢产物的能力使其具有对不同入侵病原体快速反应的优势。
