Vγ9/Vδ2 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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Abstract
Isopentenyl diphosphate (IPP), an important precursor of isoprenoid biosynthesis in prokaryotic and eukaryotic organisms, has been shown to activate Vγ9/Vδ2 T cells, the major subset of human γδ 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 Vγ9/Vδ2 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 Vγ9/Vδ2 T cells. As the amounts of IPP present in the bacterial preparations are not sufficient to induce significant Vγ9/Vδ2 T cell activation, our data suggest that compounds other than IPP associated with the DOXP pathway are responsible for Vγ9/Vδ2 T cell activation.