title: Selective inhibition of T cell activation via CD147 through novel modulation of lipid rafts.
abstract: The plasma membrane is compartmentalized into microdomains and the association/dissociation of receptors and signaling molecules with/from these membrane domains is a major principle for regulation of signal transduction. By following the reorganization of microdomains on living cells and performing biochemical studies, we show that Ab targeting of the T cell activation-associated Ag CD147 prevents TCR stimulation-dependent reorganization and clustering of microdomains. Triggering CD147 induces a displacement of the GPI-anchored coreceptors CD48 and CD59 from microdomains in human T lymphocytes. This perturbation of microdomains is accompanied by a selective inhibition of TCR-mediated T cell proliferation. The CD147-inhibited cells secret normal levels of IL-2 but acquire reduced amounts of the IL-2 receptor alpha-chain CD25. These results indicate that negative regulating signals can modulate microdomains and suggest a general mechanism for inhibition of receptor signaling.
authors.affiliation: Institute of Immunology, University of Vienna, Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Staffler
authors.forename: Andreas
authors.initials: A
authors.lastname: Szekeres
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Schütz
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Prager
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.forename: Karel
authors.initials: K
authors.lastname: Drbal
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D018106:CD28 Antigens / Q000276:immunology / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007152:Immunologic Capping / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007519:Isoantigens / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D016853:Muromonab-CD3 / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D018106:CD28 Antigens; D016207:Cytokines; D007376:Interleukin-2; D007519:Isoantigens; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018121:Receptors, Cytokine; D051926:Basigin; D019000:Phosphotyrosine