Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 3, Pages 1479-1490Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.3.1479
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Funding
- NCI NIH HHS [R01CA65979] Funding Source: Medline
- NIGMS NIH HHS [GM07185] Funding Source: Medline
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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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