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CD45 Signals outside of Lipid Rafts to Promote ERK Activation, Synaptic Raft Clustering, and IL-2 Production¹

Min Zhang^*, Miriana Moran^*, June Round^*, Teresa A. Low^*, Viresh P. Patel^*, Tamar Tomassian^*, Joseph D. Hernandez and M. Carrie Miceli^2,*,

^* Departments of Microbiology, Immunology, and Molecular Genetics, The Molecular Biology Institute, and Department of Pathology and Laboratory Medicine, University of California School of Medicine, Los Angeles, CA 90095

CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation, although the molecular consequences of CD45 repositioning remain unclear. In this study we examine the role of CD45 membrane compartmentalization in regulating murine T cell activation. We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. We propose that these dual CD45 activities ensure that only robust TCR signals proceed, whereas signals meeting threshold requirements are potentiated. Our findings highlight membrane compartmentalization as a key regulator of CD45 function and elucidate a novel signal transduction pathway by which raft-excluded CD45 positively regulates T cell activation.

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