Selective inhibition of T cell activation via CD147 through novel modulation of lipid rafts.
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.
Staffler
Günther
G
Institute of Immunology, University of Vienna, Vienna, Austria.
Szekeres
Andreas
A
Schütz
Gerhard J
GJ
Säemann
Marcus D
MD
Prager
Elisabeth
E
Zeyda
Maximilian
M
Drbal
Karel
K
Zlabinger
Gerhard J
GJ
Stulnig
Thomas M
TM
Stockinger
Hannes
H
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
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