PNNL

Abstract

Human ?d T cells containing the V?2Vd2 (V?9Vd2) T cell receptor are stimulated by a broad variety of small, phosphorus-containing antigenic molecules called “phosphoantigens”. The structures of several species present in both Mycobacteria (TUBags1-4) and in E. coli and have been reported to contain a formyl-alkyl diphosphate core. Here, we report the synthesis of the lead member of the series, 3-formyl-1-butyl diphosphate. This compound has low activity for ?d T cell stimulation, unlike its highly active isomer (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), necessitating a revision of the structure of TUBag1. Likewise, the structure of the species identified as the pentyl analog (TUBag 2) is revised to 6-phosphogluconate. These results indicate that neither TUBag1 nor the m/e 275 species proposed for TUBag2 are 3-formyl-1-alkyl diphosphates, leading to the conclusion that none of the natural phosphoantigens (TUBags1-4) possess the structures reported previously.