Structural studies of Vgamma2Vdelta2 T cell phosphoantigens

Chem Biol. 2006 Sep;13(9):985-92. doi: 10.1016/j.chembiol.2006.08.007.

Abstract

Human gammadelta T cells containing the Vgamma2Vdelta2 (Vgamma9Vdelta2) 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 Escherichia coli 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 gammadelta T cell stimulation, unlike its highly active isomer (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / immunology
  • Humans
  • Lymphocyte Activation
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mycobacterium / immunology
  • Organophosphates / chemistry*
  • Organophosphates / immunology*
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry*
  • Organophosphorus Compounds / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Vaccines, Synthetic / immunology

Substances

  • 3-formyl-1-butyl pyrophosphate
  • 4-hydroxy-3-methyl-2-butenyl diphosphate
  • Antigens, Bacterial
  • Organophosphates
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • Vaccines, Synthetic