CD4 ligation excludes the Carma1-Bcl10-MALT1 complex from GM1-positive membrane rafts in CD3/CD28 activated T cells |
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Authors: | Rigo Maxime Chentouf Myriam Pèlegrin André Chardès Thierry |
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Institution: | IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier F-34298, France;INSERM, Unit 896, Montpellier F-34298, France;Université Montpellier 1, Montpellier F-34298, France;CRLC Val d’Aurelle Paul Lamarque, Montpellier F-34298, France |
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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 24 h-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. |
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Keywords: | Abbreviations: ADCC antibody-dependent cell-mediated cytotoxicity APC antigen-presenting-cells Bcl10 B cell lymphoma 10 Carma1 caspase-recruitment domain-membrane-associated guanylate kinase protein1 CDC complement-dependent cytotoxicity EGFP enhance green fluorescent protein GM1 ganglioside M1 IL-2 interleukin 2 PKC protein kinase C MAGUK membrane-associated guanylate kinase MALT1 mucosa-associated lymphoid tissue 1 NF-κB nuclear factor-kappa B rIgG1 recombinant IgG1 TCR T cell receptors ZAP-70 zeta-chain-associated protein kinase of 70 kDa |
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