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

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.