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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 language | English |
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Pages (from-to) | 874-884 |
Number of pages | 11 |
Journal | The Journal of Immunology |
Volume | 199 |
Issue number | 3 |
Early online date | 24 Jul 2017 |
DOIs | |
Publication status | Published - 1 Aug 2017 |
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- 1 Finished
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Mechanisms that regulate T cell responses and their failure in autoimmunity
1/01/12 → 31/07/17
Project: Research