Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates its potential to activate human γδ T cells but does not lead to competitive antagonism

The immunological characterization of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), and its methylenediphosphonate analogue, HMB-PCP, is described. With an EC50 of 0.1-0.2 nM, HMB-PP is significantly more potent in stimulating human Vgamma9/Vdelta2 T cells than any other compound described so far. However, replacing the pyrophosphate by a P-CH2-P function abrogates the bioactivity drastically, with HMB-PCP having a EC50 of only 5.3 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.