title: Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling.
abstract: Activating stimuli for T lymphocytes are transmitted through plasma membrane domains that form at T-cell antigen receptor (TCR) signalling foci. Here, we determined the molecular lipid composition of immunoisolated TCR activation domains. We observed that they accumulate cholesterol, sphingomyelin and saturated phosphatidylcholine species as compared with control plasma membrane fragments. This provides, for the first time, direct evidence that TCR activation domains comprise a distinct molecular lipid composition reminiscent of liquid-ordered raft phases in model membranes. Interestingly, TCR activation domains were also enriched in plasmenyl phosphatidylethanolamine and phosphatidylserine. Modulating the T-cell lipidome with polyunsaturated fatty acids impaired the plasma membrane condensation at TCR signalling foci and resulted in a perturbed molecular lipid composition. These results correlate the accumulation of specific molecular lipid species with the specific plasma membrane condensation at sites of TCR activation and with early TCR activation responses.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Zech
authors.forename: Christer S
authors.initials: CS
authors.lastname: Ejsing
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.forename: Ben
authors.initials: B
authors.lastname: de Wet
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Kai
authors.initials: K
authors.lastname: Simons
authors.forename: Thomas
authors.initials: T
authors.lastname: Harder
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; D013109:Sphingomyelins; D002784:Cholesterol