Cutting edge: phosphatidylinositol 4,5-bisphosphate concentration at the APC side of the immunological synapse is required for effector T cell function.
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.
Fooksman
David Robert
DR
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. fooksman@saturn.med.nyu.edu
Shaikh
Saame Raza
SR
Boyle
Sarah
S
Edidin
Michael
M
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*
D019269:Phosphatidylinositol 4,5-Diphosphate