Microbial isoprenoid biosynthesis and human gammadelta T cell activation.

Matthias Eberl, Martin Hintz, Armin Reichenberg, Ann-Kristin Kollas, Jochen Wiesner, Hassan Jomaa

Journal: FEBS letters 2003;544(1-3):4-10

PMID: 12782281

Abstract

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.

Address: Biochemisches Institut, Justus-Liebig-Universität Giessen, Friedrichstr. 24, Germany. [email protected]

DOI: 10.1016/s0014-5793(03)00483-6