IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier F-34298, France.
Cell Immunol. 2011;270(1):40-6. doi: 10.1016/j.cellimm.2011.03.025. Epub 2011 Mar 29.
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.
抗体 13B8.2 靶向 CD4 蛋白 D1 结构域上的 CDR3 样环，可诱导 CD4/ZAP-70 重排并在质膜筏中释放神经酰胺。在这里，我们研究了 13B8.2 是否可以通过影响质膜筏中的 Carma1-Bcl10-MALT1 复合物来介导 CD4/ZAP-70 的区室化。我们报告说，用 13B8.2 而非利妥昔单抗处理 CD3/CD28 激活的 Jurkat T 细胞可将 Carma1-Bcl10-MALT1 蛋白从 GM1(+)质膜筏中排除，并同时降低 NF-κB 激活。荧光共聚焦成像证实，CD3/CD28 激活后在 GM1(+)质膜筏中观察到的 Carma1-Bcl10 和 Carma1-MALT1 共定位，在 13B8.2 处理 24 小时后被消除。因此，13B8.2 诱导的 CD4/ZAP-70 在质膜筏中的区室化与 Carma1-Bcl10-MALT1 筏排除有关。
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