Microbial isoprenoid biosynthesis and human gammadelta T cell activation.
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.
Eberl
Matthias
M
Biochemisches Institut, Justus-Liebig-Universität Giessen, Friedrichstr. 24, Germany. matthias.eberl@biochemie.med.uni-giessen.de
Hintz
Martin
M
Reichenberg
Armin
A
Kollas
Ann-Kristin
AK
Wiesner
Jochen
J
Jomaa
Hassan
H
D000941:Antigens / Q000737:chemistry; D001419:Bacteria / Q000472:pathogenicity*; D002460:Cell Line; D011756:Diphosphates / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation; D008956:Models, Chemical; D009154:Mutation; D011105:Polyisoprenyl Phosphate Sugars / Q000737:chemistry*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology*
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D000941:Antigens; D011756:Diphosphates; D011105:Polyisoprenyl Phosphate Sugars; D016692:Receptors, Antigen, T-Cell, gamma-delta