Caveolin-1 orchestrates TCR synaptic polarity, signal specificity, and function in CD8 T cells |
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Authors: | Tomassian Tamar Humphries Lisa A Liu Scot D Silva Oscar Brooks David G Miceli M Carrie |
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Institution: | Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine and College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. |
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Abstract: | TCR engagement triggers the polarized recruitment of membrane, actin, and transducer assemblies within the T cell-APC contact that amplify and specify signaling cascades and T effector activity. We report that caveolin-1, a scaffold that regulates polarity and signaling in nonlymphoid cells, is required for optimal TCR-induced actin polymerization, synaptic membrane raft polarity, and function in CD8, but not CD4, T cells. In CD8(+) T cells, caveolin-1 ablation selectively impaired TCR-induced NFAT-dependent NFATc1 and cytokine gene expression, whereas caveolin-1 re-expression promoted NFATc1 gene expression. Alternatively, caveolin-1 ablation did not affect TCR-induced NF-κB-dependent Iκbα expression. Cav-1(-/-) mice did not efficiently promote CD8 immunity to lymphocytic choriomeningitis virus, nor did cav-1(-/-) OT-1(+) CD8(+) T cells efficiently respond to Listeria monocytogenes-OVA after transfer into wild-type hosts. Therefore, caveolin-1 is a T cell-intrinsic orchestrator of TCR-mediated membrane polarity and signal specificity selectively employed by CD8 T cells to customize TCR responsiveness. |
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