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Microbial isoprenoid biosynthesis and human gammadelta T cell activation
Matthias Eberl1, Martin Hintz, Armin Reichenberg
1Biochemisches Institut, Justus-Liebig-Universität Giessen, Friedrichstr. 24, Germany. matthias.eberl@biochemie.med.uni-giessen.de
FEBS Letters
|June 5, 2003
Summary
Human Vgamma9/Vdelta2 T cells are activated by (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMB-PP), an intermediate from the bacterial isoprenoid biosynthesis pathway. This finding explains their response to non-peptide antigens.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Human Vgamma9/Vdelta2 T cells are vital for immunity against pathogens.
- Their reactivity to non-peptide antigens remained unexplained.
- The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway is essential for isoprenoid biosynthesis in many bacteria.
Purpose of the Study:
- To elucidate the mechanism behind Vgamma9/Vdelta2 T cell activation by non-peptide antigens.
- To identify the specific microbial metabolite responsible for this T cell response.
Main Methods:
- Investigated the link between the MEP pathway intermediates and T cell activation.
- Utilized knowledge from the elucidation of the MEP pathway's reaction steps.
- Assessed the potency of MEP pathway intermediates as T cell activators.
Main Results:
- Identified (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMB-PP), an intermediate of the MEP pathway, as a potent activator.
- HMB-PP demonstrated exceptionally high potency, with an EC50 of 0.1 nM.
- This discovery provides a molecular basis for Vgamma9/Vdelta2 T cell recognition of microbial metabolites.
Conclusions:
- The MEP pathway intermediate HMB-PP is the primary activator of human Vgamma9/Vdelta2 T cells.
- This finding bridges the fields of immunology and bacterial biochemistry.
- It explains the unconventional reactivity of these T cells towards microbial pathogens.