Escherichia coli Produces Phosphoantigens Activating Human γδ T Cells

• Published in: The Journal of biological chemistry 2002-01, Vol.277 (1), p.148-154
• Main Authors: Feurle, Juliane, Espinosa, Eric, Eckstein, Susanne, Pont, Frédéric, Kunzmann, Volker, Fournié, Jean-Jacques, Herderich, Markus, Wilhelm, Martin
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M106443200

Human Vγ9δ2 T lymphocytes are suggested to play an important role in the immune response to various microbial pathogens. In contrast to αβ T cells, γδ 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 γδ 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 γδ T cell-stimulating capacity of Escherichia coli as similar to the mycobacterial phosphoantigens 3-formyl-1-butyl-pyrophosphate and itsMr 275 homologue TUBag2. In addition,E. coli phosphoantigens exert bioactivities on γδ 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 γδ T lymphocytes.