Human gamma-delta T cells are activated by intermediates of the the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis

Abstract

Activation of Vγ9/Vδ2 T cells by small nonprotein Ags is frequently observed after infection with various viruses, bacteria, and eukaryotic parasites. We suggested earlier that compounds synthesized by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway of isopentenyl pyrophosphate synthesis are responsible for the Vγ9/Vδ2 T cell reactivity of many pathogens. Using genetically engineered Escherichia coli knockout strains, we now demonstrate that the ability of E. coli extracts to stimulate γδ T cell proliferation is abrogated when genes coding for essential enzymes of the MEP pathway, dxr or gcpE, are disrupted or deleted from the bacterial genome.