In addition to antigen presentation to CD4⁺ T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of MHC-II, which was associated with decreased surface expression levels in murine dendritic cells (DCs) and resulted in impaired activation of CD4⁺ T cells. However, the downstream signal that induces MHC-II endocytosis remains to be elucidated. In this study, we found that the crosslinking of MHC-II induced intracellular Ca²⁺ mobilization, which was necessary for crosslinking-induced MHC-II endocytosis. We also found that these events were suppressed by inhibitors of Syk and phospholipase C (PLC). Treatments with a phorbol ester promoted MHC-II endocytosis, whereas inhibitors of protein kinase C (PKC) suppressed crosslinking-induced endocytosis of MHC-II. These results suggest that PKC could be involved in this process. Furthermore, crosslinking-induced MHC-II endocytosis was suppressed by inhibitors of clathrin-dependent endocytosis. Our results indicate that the crosslinking of MHC-II could stimulate Ca²⁺ mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs.

中文翻译：

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MHC II 类连接诱导 PKC 依赖性网格蛋白介导的 MHC II 类内吞作用。


除了向 CD4 ⁺ T 细胞呈递抗原外，细胞表面主要组织相容性复合物 II 类 (MHC-II) 分子的聚集还会诱导抗原呈递细胞中的信号转导，从而调节细胞功能。我们之前报道过，MHC-II 的交联诱导了 MHC-II 的内吞作用，这与鼠树突状细胞 (DC) 表面表达水平降低有关，并导致 CD4 ⁺ T 细胞的活化受损。然而，诱导 MHC-II 内吞作用的下游信号仍有待阐明。在本研究中，我们发现MHC-II 的交联诱导细胞内Ca ²⁺动员，这对于交联诱导的MHC-II 内吞作用是必需的。我们还发现这些事件被 Syk 和磷脂酶 C (PLC) 抑制剂抑制。佛波酯处理促进 MHC-II 内吞作用，而蛋白激酶 C (PKC) 抑制剂则抑制交联诱导的 MHC-II 内吞作用。这些结果表明 PKC 可能参与这一过程。此外，交联诱导的 MHC-II 内吞作用被网格蛋白依赖性内吞作用抑制剂抑制。我们的结果表明，MHC-II 的交联可以刺激 Ca ²⁺动员并诱导小鼠 DC 中 MHC-II 的网格蛋白依赖性内吞作用。