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

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

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)874-884
Number of pages11
JournalJournal of Immunology
Volume199
Issue number3
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

Cite this

Borger, J. G., Morrison, V. L., Filby, A., Garcia, C., Uotila, L. M., Simbari, F., ... Zamoyska, R. (2017). Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells. Journal of Immunology, 199(3), 874-884. https://doi.org/10.4049/jimmunol.1700431
Borger, Jessica G. ; Morrison, Vicky L. ; Filby, Andrew ; Garcia, Celine ; Uotila, Liisa M. ; Simbari, Fabio ; Fagerholm, Susanna C. ; Zamoyska, Rose. / Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells. In: Journal of Immunology. 2017 ; Vol. 199, No. 3. pp. 874-884.
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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.",
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Borger, JG, Morrison, VL, Filby, A, Garcia, C, Uotila, LM, Simbari, F, Fagerholm, SC & Zamoyska, R 2017, 'Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells', Journal of Immunology, vol. 199, no. 3, pp. 874-884. https://doi.org/10.4049/jimmunol.1700431

Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells. / Borger, Jessica G.; Morrison, Vicky L.; Filby, Andrew; Garcia, Celine; Uotila, Liisa M.; Simbari, Fabio; Fagerholm, Susanna C.; Zamoyska, Rose.

In: Journal of Immunology, Vol. 199, No. 3, 01.08.2017, p. 874-884.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Borger, Jessica G.

AU - Morrison, Vicky L.

AU - Filby, Andrew

AU - Garcia, Celine

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AU - Simbari, Fabio

AU - Fagerholm, Susanna C.

AU - Zamoyska, Rose

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N2 - 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.

AB - 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.

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