Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human γδ T cells
Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human γδ T cells
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DOI：
10.1074/jbc.m100495200
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发表时间：
2001-05-25
影响因子：
4.8
通讯作者：
Fournié, JJ
中科院分区：
文献类型：
--
作者：
Espinosa, E;Belmant, C;Fournié, JJ
来自分枝杆菌的小磷酸化代谢物刺激人γ δ T淋巴细胞。虽然这种磷酸化抗原可以证明在涉及γ δ T细胞介导的免疫的疫苗组合物中是有用的，但它们在天然来源中的丰度非常低，限制了这种应用。在这里，我们描述的化学生产，纯化，和生物活性的磷酸化溴代醇（BrHPP）类似物，模仿天然磷酸化抗原的生物学特性，这种化合物可以获得克量，易于检测，并在水溶液中的高稳定性。然而，即使在微摩尔浓度下也没有检测到BrHPP与广泛的细胞表面受体的非特异性结合，纳摩尔浓度特异性地触发人γ δ T淋巴细胞的效应子应答。因此，BrHPP是能够有效免疫刺激人γ δ T淋巴细胞的新型分子。
Small phosphorylated metabolites from mycobacteria stimulate human gamma delta T lymphocytes. Although such phosphoantigens could prove useful in the composition of vaccines involving gamma delta T cell-mediated immunity, their very low abundance in natural sources limits such applications. Here, we describe the chemical production, purification, and bioactivity of a phosphorylated bromohydrin (BrHPP) analogue that mimics the biological properties of natural phosphoantigens, This compound can be obtained in gram amounts, is easy to detect, and is of high stability in aqueous solutions. Whereas unspecific binding of BrHPP to a wide panel of cell surface receptors is not detected even at micromolar concentrations, nanomolar concentrations specifically trigger effector responses of human gamma delta T lymphocytes, Thus, BrHPP is a novel molecule enabling potent immunostimulation of human gamma delta T lymphocytes.