title: Caveolin-1 orchestrates TCR synaptic polarity, signal specificity, and function in CD8 T cells.
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.
authors.affiliation: 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.
authors.forename: Tamar
authors.initials: T
authors.lastname: Tomassian
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Humphries
authors.forename: Scot D
authors.initials: SD
authors.lastname: Liu
authors.forename: Oscar
authors.initials: O
authors.lastname: Silva
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
authors.forename: M Carrie
authors.initials: MC
authors.lastname: Miceli
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051242:Caveolin 1 / Q000276:immunology* / Q000378:metabolism; D016764:Cell Polarity; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D015151:Immunoblotting; D054992:Immunological Synapses / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000199:Actins; D051242:Caveolin 1; D011948:Receptors, Antigen, T-Cell