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Caveolin-1 Influences LFA-1 Redistribution upon TCR Stimulation in CD8 T Cells

TCR stimulation by peptide–MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membr...

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Detalles Bibliográficos
Autores principales: Borger, Jessica G., Morrison, Vicky L., Filby, Andrew, Garcia, Celine, Uotila, Liisa M., Simbari, Fabio, Fagerholm, Susanna C., Zamoyska, Rose
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523581/
https://www.ncbi.nlm.nih.gov/pubmed/28637901
http://dx.doi.org/10.4049/jimmunol.1700431
Descripción
Sumario:TCR stimulation by peptide–MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organization of signal transduction pathways. The presence of Cav1 protein in T cells was identified only recently, and its function in this context is not well understood. We show that Cav1-knockout CD8 T cells have a reduction in membrane cholesterol and sphingomyelin, and upon TCR triggering they exhibit altered morphology and polarity, with reduced effector function compared with Cav1 wild-type CD8 T cells. In particular, redistribution of the β(2) integrin LFA-1 to the immunological synapse is compromised in Cav1-knockout T cells, as is the ability of LFA-1 to form high-avidity interactions with ICAM-1. Our results identify a role for Cav1 in membrane organization and β(2) integrin function in primary CD8 T cells.