Vgamma9/Vdelta2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis.

Vgamma9/Vdelta2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis.
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细菌低分子量化合物诱导的 Vgamma9/Vdelta2 T 细胞活化取决于类异戊二烯生物合成的 1-脱氧-D-木酮糖 5-磷酸途径。

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发表时间:
1999
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通讯作者:
M. Wilhelm
M. Wilhelm
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作者:
H. Jomaa;J. Feurle;K. Lühs;V. Kunzmann;H. Tony;M. Herderich;M. Wilhelm

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异戊烯基二磷酸(IPP)是原核生物和真核生物中类异戊二烯生物合成的重要前体,已显示激活人γ δ T细胞的主要亚群V γ 9/V δ 2 T细胞。IPP的生物合成首先被描述为乙酸/甲羟戊酸途径。最近,1-脱氧-D-木酮糖5-磷酸(DOXP)和2-C-甲基-D-β 4-磷酸已被证明是DOXP途径中的关键代谢物,也导致在一些真细菌如大肠杆菌中形成IPP。在这里,我们报告说,低分子质量分数的提取物从细菌使用DOXP途径诱导Vgamma 9/Vdelta 2 T细胞活化,而类似的制剂从细菌使用经典的甲羟戊酸途径不能做到这一点。1-脱氧-D-木酮糖的加入增强了E. coli提取物以活化V γ 9/V δ 2 T细胞。由于存在于细菌制剂中的IPP的量不足以诱导显著的V γ 9/Vdelta 2 T细胞活化,我们的数据表明,与DOXP途径相关的IPP以外的化合物负责V γ 9/Vdelta 2 T细胞活化。
Isopentenyl diphosphate (IPP), an important precursor of isoprenoid biosynthesis in prokaryotic and eukaryotic organisms, has been shown to activate Vgamma9/Vdelta2 T cells, the major subset of human gammadelta T cells. The biosynthesis of IPP has been first described as the acetate/mevalonate pathway. Recently, 1-deoxy-D-xylulose 5-phosphate (DOXP) and 2-C-methyl-D-erythritol 4-phosphate have been shown to be key metabolites in the DOXP pathway also leading to the formation of IPP in some eubacteria such as Escherichia coli. Here we report that the low molecular mass fraction of extracts from bacteria using the DOXP pathway induces Vgamma9/Vdelta2 T cell activation, while analogous preparations from bacteria using the classical mevalonate pathway fail to do so. Addition of 1-deoxy-D-xylulose potentiates the ability of E. coli extracts to activate Vgamma9/Vdelta2 T cells. As the amounts of IPP present in the bacterial preparations are not sufficient to induce significant Vgamma9/Vdelta2 T cell activation, our data suggest that compounds other than IPP associated with the DOXP pathway are responsible for Vgamma9/Vdelta2 T cell activation.