Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells

Jessica Borger, Vicky L Morrison, Andrew Filby, Celine Garcia, Liisa M Uotila, Fabio Simbari, Susanna C Fagerholm, Rose Zamoyska

Research output: Contribution to journalArticlepeer-review

Abstract

T cell receptor (TCR) stimulation by pMHC complexes on antigen presenting cells (APC), requires precise re-organisation of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin-1 (Cav1), a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organisation 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 (KO) CD8 T cells have a reduction in membrane cholesterol and sphingomyelin, and upon TCR triggering exhibit altered morphology and polarity, with reduced effector function compared to Cav-1 wild-type CD8 T cells. In particular, redistribution of the β2 integrin, LFA-1, to the immunological synapse is compromised in Cav1KO 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 organisation and β2 integrin function in primary CD8 T cells.
Original languageEnglish
Pages (from-to)874-884
Number of pages11
JournalJournal of Immunology
Volume199
Issue number3
Early online date24 Jul 2017
DOIs
Publication statusPublished - 1 Aug 2017

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