Repertoire Development and the Control of Cytotoxic/Effector Function in Human T Cells
Figure 2
Human 2Vδ2 T cells respond to stimulatory phosphoantigens produced during bacterial or mammalian isoprenoid synthesis. Isoprenoid synthesis in many prokaryotes and protists produces the intermediate (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) from pyruvate and glyceraldehyde 3-phosphate via the erythritol 4 phosphate pathway. Eukaryotes use the mevalonate pathway that produces isoprenoids and colesterol. HMBPP and IPP are phosphoantigens; HMBPP is unique to the erythritol 4 phosphate pathway while IPP is produced in both pathways. Phosphoantigens stimulate cytokine secretion and cytotoxicity in human 2Vδ2 T cells. Statins block the eukaryotic pathway prior to mevalonate synthesis, and decrease the production of IPP. Bisphosphonates are a class of drugs that inhibit farnesyl pyrophosphate synthase and cause the accumulation of IPP in mammalian cells. When mammalian cells of myeloid origin and some tumor cells are treated with bisphosphonate, they are more stimulatory for 2V2 T cells due to increased IPP production.
