title: CD4 ligation excludes the Carma1-Bcl10-MALT1 complex from GM1-positive membrane rafts in CD3/CD28 activated T cells.
abstract: The antibody 13B8.2, which is directed against the CDR3-like loop on the D1 domain of CD4, induces CD4/ZAP-70 reorganization and ceramide release in membrane rafts. Here, we investigated whether CD4/ZAP-70 compartmentalization could be mediated by an effect of 13B8.2 on the Carma1-Bcl10-MALT1 complex in membrane rafts. We report that treatment of CD3/CD28-activated Jurkat T cells with 13B8.2, but not rituximab, excluded Carma1-Bcl10-MALT1 proteins from GM1(+) membrane rafts and concomitantly decreased NF-κB activation. Fluorescence confocal imaging confirmed that Carma1-Bcl10 and Carma1-MALT1 co-patching, observed in GM1(+) membrane rafts following CD3/CD28 activation, were abrogated after a 24h-treatment with 13B8.2. The CD4/ZAP-70 compartmentalization in membrane rafts induced by 13B8.2 is thus related to Carma1-Bcl10-MALT1 raft exclusion.
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier F-34298, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Rigo
authors.forename: Myriam
authors.initials: M
authors.lastname: Chentouf
authors.forename: André
authors.initials: A
authors.lastname: Pèlegrin
authors.forename: Thierry
authors.initials: T
authors.lastname: Chardès
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000911:Antibodies, Monoclonal; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D006162:Guanylate Cyclase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology / Q000378:metabolism
chemical_list: C110023:13B8-2 monoclonal antibody; D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D009363:Neoplasm Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C426242:CARD11 protein, human; D006162:Guanylate Cyclase