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.