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

Borger, J. G., Morrison, V. L., Filby, A., Garcia, C., Uotila, L. M., Simbari, F., Fagerholm, S. C. and Zamoyska, R. (2017) Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells. Journal of Immunology, 199(3), pp. 874-884. (doi:10.4049/jimmunol.1700431) (PMID:28637901) (PMCID:PMC5523581)

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Abstract

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 β2 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 β2 integrin function in primary CD8 T cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Vicky
Authors: Borger, J. G., Morrison, V. L., Filby, A., Garcia, C., Uotila, L. M., Simbari, F., Fagerholm, S. C., and Zamoyska, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:21 June 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Immunology 199(3):874-884
Publisher Policy:Reproduced under a Creative Commons License

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