Functional implications of plasma membrane condensation for T cell activation.
The T lymphocyte plasma membrane condenses at the site of activation but the functional significance of this receptor-mediated membrane reorganization is not yet known. Here we demonstrate that membrane condensation at the T cell activation sites can be inhibited by incorporation of the oxysterol 7-ketocholesterol (7KC), which is known to prevent the formation of raft-like liquid-ordered domains in model membranes. We enriched T cells with 7KC, or cholesterol as control, to assess the importance of membrane condensation for T cell activation. Upon 7KC treatment, T cell antigen receptor (TCR) triggered calcium fluxes and early tyrosine phosphorylation events appear unaltered. However, signaling complexes form less efficiently on the cell surface, fewer phosphorylated signaling proteins are retained in the plasma membrane and actin restructuring at activation sites is impaired in 7KC-enriched cells resulting in compromised downstream activation responses. Our data emphasizes lipids as an important medium for the organization at T cell activation sites and strongly indicates that membrane condensation is an important element of the T cell activation process.
Centre for Vascular Research, University of New South Wales and the Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Carles
C
Rentero
Tobias
T
Zech
Carmel M
CM
Quinn
Karin
K
Engelhardt
David
D
Williamson
Thomas
T
Grewal
Wendy
W
Jessup
Thomas
T
Harder
Katharina
K
Gaus
D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007653:Ketocholesterols / Q000008:administration & dosage; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
D007653:Ketocholesterols; C003001:7-ketocholesterol