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.
Jomaa Pharmaka GmbH, Giessen, Germany. boran.altincicek@biochemie.med.uni-giessen.de
B
B
Altincicek
J
J
Moll
N
N
Campos
G
G
Foerster
E
E
Beck
J F
JF
Hoeffler
C
C
Grosdemange-Billiard
M
M
Rodríguez-Concepción
M
M
Rohmer
A
A
Boronat
M
M
Eberl
H
H
Jomaa
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