TY - JOUR
T1 - Caveolin-1 influences LFA-1 redistribution upon TCR stimulation in CD8 T cells
AU - Borger, Jessica G.
AU - Morrison, Vicky L.
AU - Filby, Andrew
AU - Garcia, Celine
AU - Uotila, Liisa M.
AU - Simbari, Fabio
AU - Fagerholm, Susanna C.
AU - Zamoyska, Rose
PY - 2017/8/1
Y1 - 2017/8/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85026258746&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1700431
DO - 10.4049/jimmunol.1700431
M3 - Article
AN - SCOPUS:85026258746
SN - 0022-1767
VL - 199
SP - 874
EP - 884
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -