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Cutting Edge: Phosphatidylinositol 4,5-Bisphosphate Concentration at the APC Side of the Immunological Synapse Is Required for Effector T Cell Function¹

David Robert Fooksman^2,3,*, Saame Raza Shaikh^2,, Sarah Boyle^* and Michael Edidin^*

^* Department of Biology, Johns Hopkins University, Baltimore, MD 21218; and Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834

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)P₂) at the APC side of the immunological synapse. In both human and mouse cells, a PI(4,5)P₂-specific fluorescent reporter, PH-GFP (where PH is pleckstrin homology), detected an Ag-dependent enrichment of PI(4,5)P₂ at the synapse between Ag-specific T cells and APC. When PIP(4,5)P₂ 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by National Institutes of Health Grant AI-14584 (to M.E.) and National Institutes of Health Training Grant 5T32 AI-07247 (to S.R.S.).

² D.R.F. and S.R.S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. David Robert Fooksman at the current address: Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail address: fooksman{at}saturn.med.nyu.edu

⁴ Abbreviations used in this paper: IS, immunological synapse; PH, pleckstrin homology; PI(4,5)P₂, phosphatidylinositol 4,5-bisphosphate.

⁵ The online version of this article contains supplemental material.