Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis.
Activation of V gamma 9/V delta 2 T cells by small nonprotein Ags is frequently observed after infection with various viruses, bacteria, and eukaryotic parasites. We suggested earlier that compounds synthesized by the 2-C:-methyl-D-erythritol 4-phosphate (MEP) pathway of isopentenyl pyrophosphate synthesis are responsible for the V gamma 9/V delta 2 T cell reactivity of many pathogens. Using genetically engineered Escherichia coli knockout strains, we now demonstrate that the ability of E. coli extracts to stimulate gamma delta T cell proliferation is abrogated when genes coding for essential enzymes of the MEP pathway, dxr or gcpE, are disrupted or deleted from the bacterial genome.
Altincicek
B
B
Jomaa Pharmaka GmbH, Giessen, Germany. boran.altincicek@biochemie.med.uni-giessen.de
Moll
J
J
Campos
N
N
Foerster
G
G
Beck
E
E
Hoeffler
J F
JF
Grosdemange-Billiard
C
C
Rodríguez-Concepción
M
M
Rohmer
M
M
Boronat
A
A
Eberl
M
M
Jomaa
H
H
D019747:Aldose-Ketose Isomerases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002458:Cell Fractionation; D004798:Enzymes; D004896:Erythritol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000502:physiology; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D045782:Hemiterpenes; D006801:Humans; D008213:Lymphocyte Activation; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000235:genetics; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics; D015202:Protein Engineering; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013403:Sugar Phosphates / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology
C114232:2-C-methylerythritol 4-phosphate; D001426:Bacterial Proteins; D004798:Enzymes; D045782:Hemiterpenes; D009097:Multienzyme Complexes; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013403:Sugar Phosphates; C421242:hydroxymethylbutenyl 4-diphosphate synthase; C004809:isopentenyl pyrophosphate; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; D004896:Erythritol