title: Escherichia coli produces phosphoantigens activating human gamma delta T cells.
abstract: Human Vgamma9delta2 T lymphocytes are suggested to play an important role in the immune response to various microbial pathogens. In contrast to alphabeta T cells, gammadelta T lymphocytes recognize small, non-protein, phosphate-bearing antigens (phosphoantigens) in a major histocompatibility complex-independent manner. Four different phosphoantigens termed TUBag1 to TUBag4 with a common 3-formyl-1-butyl-pyrophosphate moiety and isopentenyl-pyrophosphate have been isolated and identified from mycobacteria. However, natural occurring gammadelta T cell ligands from other bacterial species were not characterized so far. Here, we describe the structural identification of the two compounds responsible for the gammadelta T cell-stimulating capacity of Escherichia coli as similar to the mycobacterial phosphoantigens 3-formyl-1-butyl-pyrophosphate and its M(r) 275 homologue TUBag2. In addition, E. coli phosphoantigens exert bioactivities on gammadelta T cells with similar potencies to the mycobacterial phosphoantigens at 5-15 nm concentration. Furthermore, our results clearly prove that the deoxyxylulose 5-phophate pathway (also referred to as Rohmer metabolic route of isoprenoid biosynthesis) is essential for the biosynthesis of the phosphoantigens in E. coli. Because this pathway is absent from human cells, it proves an ideal target for focusing efficiently the antimicrobial selectivity of human gammadelta T lymphocytes.
authors.affiliation: Medizinische Poliklinik der Universitaet Wuerzburg, Klinikstrasse 6-8, 97070 Wuerzburg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Feurle
authors.forename: Eric
authors.initials: E
authors.lastname: Espinosa
authors.forename: Susanne
authors.initials: S
authors.lastname: Eckstein
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pont
authors.forename: Volker
authors.initials: V
authors.lastname: Kunzmann
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Markus
authors.initials: M
authors.lastname: Herderich
authors.forename: Martin
authors.initials: M
authors.lastname: Wilhelm
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D002460:Cell Line; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008970:Molecular Weight; D010750:Phosphoproteins / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta