HMB-PP

HMB-PP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate) is a potent phosphoantigen and an intermediate in the non-mevalonate pathway (MEP pathway) of isoprenoid biosynthesis, which is present in many bacteria and protozoa but absent in humans. It acts as a highly specific and potent activator of human Vγ9Vδ2 T cells, a subset of gamma-delta T cells that play a crucial role in the innate-like immune response against pathogens and tumors. By binding to the intracellular B30.2 domain of butyrophilin 3A1 (BTN3A1), HMB-PP triggers a conformational change that is recognized by the Vγ9Vδ2 T-cell receptor, leading to the activation and proliferation of these T cells. This activation results in the production of pro-inflammatory cytokines such as IFN-γ and TNF-α, as well as IL-22, which promotes mucosal barrier integrity. In the context of Crohn's disease, HMB-PP has been shown to stimulate Vδ2+ T-cell-mediated suppression of fungal invasion (e.g., Candida albicans) in the gut epithelium. While primarily used as a research tool, HMB-PP and its synthetic analogs are being investigated for their potential as immunotherapeutic agents and vaccine adjuvants.

Other names

(E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate(E)-4-hydroxy-3-methyl-2-butenyl diphosphatephosphoantigen