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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-\u03baB\u2013dependent I\u03bab\u03b1 expression. Cav-1\u2212\/\u2212 mice did not efficiently promote CD8 immunity to lymphocytic choriomeningitis virus, nor did cav-1\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1101447","type":"journal-article","created":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T17:07:53Z","timestamp":1314032873000},"page":"2993-3002","source":"Crossref","is-referenced-by-count":58,"title":["Caveolin-1 Orchestrates TCR Synaptic Polarity, Signal Specificity, and Function in CD8 T Cells"],"prefix":"10.1093","volume":"187","author":[{"given":"Tamar","family":"Tomassian","sequence":"first","affiliation":[{"name":"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"},{"name":"Molecular Biology Institute, University of California , Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Humphries","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scot D","family":"Liu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Silva","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Brooks","sequence":"additional","affiliation":[{"name":"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"},{"name":"Molecular Biology Institute, University of California , Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Carrie","family":"Miceli","sequence":"additional","affiliation":[{"name":"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"},{"name":"Molecular Biology Institute, University of California , Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,15]]},"reference":[{"key":"2025032410362922900_r1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/nri1647","article-title":"Tuning immune responses: diversity and adaptation of the immunological synapse","volume":"5","author":"Friedl","year":"2005","journal-title":"Nat. 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