title: Cutting edge: phosphatidylinositol 4,5-bisphosphate concentration at the APC side of the immunological synapse is required for effector T cell function.
abstract: Little is known about the signaling that occurs in an APC during contact with a T cell. In this article we report the concentration of the signaling lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) at the APC side of the immunological synapse. In both human and mouse cells, a PI(4,5)P(2)-specific fluorescent reporter, PH-GFP (where PH is pleckstrin homology), detected an Ag-dependent enrichment of PI(4,5)P(2) at the synapse between Ag-specific T cells and APC. When PIP(4,5)P(2) was sequestered by a high concentration of PH-GFP reporter, cells were less susceptible to CTL-mediated lysis than control cells. These findings suggest a new regulatory target for modulating immune function that may be exploited for immune escape by pathogens and tumors.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. fooksman@saturn.med.nyu.edu
authors.forename: David Robert
authors.initials: DR
authors.lastname: Fooksman
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Sarah
authors.initials: S
authors.lastname: Boyle
authors.forename: Michael
authors.initials: M
authors.lastname: Edidin
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate