Microbial isoprenoid biosynthesis and human gammadelta T cell activation

FEBS Lett. 2003 Jun 5;544(1-3):4-10. doi: 10.1016/s0014-5793(03)00483-6.


Human Vgamma9/Vdelta2 T cells play a crucial role in the immune response to microbial pathogens, yet their unconventional reactivity towards non-peptide antigens has been enigmatic until recently. The break-through in identification of the specific activator was only possible due to recent success in a seemingly remote field: the elucidation of the reaction steps of the newly discovered 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway of isoprenoid biosynthesis that is utilised by many pathogenic bacteria. Unexpectedly, the intermediate of the MEP pathway, (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate) (HMB-PP), turned out to be by far the most potent Vgamma9/Vdelta2 T cell activator known, with an EC(50) of 0.1 nM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens / chemistry
  • Bacteria / pathogenicity*
  • Cell Line
  • Diphosphates / chemistry*
  • Dose-Response Relationship, Drug
  • Escherichia coli / genetics
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Models, Chemical
  • Mutation
  • Polyisoprenyl Phosphate Sugars / chemistry*
  • Receptors, Antigen, T-Cell, gamma-delta / chemistry*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / microbiology*


  • 4-hydroxy-3-methylbut-2-enyl pyrophosphate
  • Antigens
  • Diphosphates
  • Polyisoprenyl Phosphate Sugars
  • Receptors, Antigen, T-Cell, gamma-delta