Escherichia coli produces phosphoantigens activating human γδ T cells
Escherichia coli produces phosphoantigens activating human γδ T cells
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DOI：
10.1074/jbc.m106443200
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发表时间：
2002-01-04
影响因子：
4.8
通讯作者：
Wilhelm, M
中科院分区：
文献类型：
--
作者：
Feurle, J;Espinosa, E;Wilhelm, M
提示人VGamma9delta2T淋巴细胞在对多种微生物病原体的免疫应答中起重要作用。与Alphabeta T细胞不同，Gammadelta T淋巴细胞以一种主要组织相容性复合体不依赖的方式识别小的、非蛋白质的、含磷的抗原(磷抗原)。从分枝杆菌中分离和鉴定了四种不同的磷抗原TUBag1~TUBag4，它们含有共同的3-甲酰基-1-丁基-焦磷酸和异戊烯-焦磷酸。然而，到目前为止，来自其他细菌物种的自然产生的Gammadelta T细胞配体还没有得到表征。在这里，我们描述了两个与大肠杆菌的Gammadelta T细胞刺激能力有关的化合物的结构鉴定，它们与分枝杆菌磷抗原3-甲酰基-1-丁基焦磷酸及其M-r275同系物TUBag2相似。此外，在5-15 nm的浓度范围内，大肠杆菌磷抗原对Gammadelta T细胞具有与分枝杆菌磷抗原相似的生物活性。此外，我们的结果清楚地证明了脱氧木糖5-磷酸途径(也被称为类异戊二烯生物合成的Rohmer代谢途径)是大肠杆菌中磷抗原生物合成所必需的。由于这条途径在人类细胞中是不存在的，它被证明是有效地集中人Gammadelta T淋巴细胞的抗微生物选择性的理想靶点。
Human Vgamma9delta2 T lymphocytes are suggested to play an important role in the immune response to various microbial pathogens. In contrast to alphabeta T cells, gammadelta T lymphocytes recognize small, non-protein, phosphate-bearing antigens (phosphoantigens) in a major histocompatibility complex-independent manner. Four different phosphoantigens termed TUBag1 to TUBag4 with a common 3-formyl-1-butyl-pyrophosphate moiety and isopentenyl-pyrophosphate have been isolated and identified from mycobacteria. However, natural occurring gammadelta T cell ligands from other bacterial species were not characterized so far. Here, we describe the structural identification of the two compounds responsible for the gammadelta T cell-stimulating capacity of Escherichia coli as similar to the mycobacterial phosphoantigens 3-formyl-1-butylpyrophosphate and its M-r 275 homologue TUBag2. In addition, E. coli phosphoantigens exert bioactivities on gammadelta T cells with similar potencies to the mycobacterial phosphoantigens at 5-15 nm concentration. Furthermore, our results clearly prove that the deoxyxylulose 5-phophate pathway (also referred to as Rohmer metabolic route of isoprenoid biosynthesis) is essential for the biosynthesis of the phosphoantigens in E. coli. Because this pathway is absent from human cells, it proves an ideal target for focusing efficiently the antimicrobial selectivity of human gammadelta T lymphocytes.