MDPI Acta Medica Okayama 2073-4409 9 8 2020 Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II 1810 EN Kento Masaki Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuhji Hiraki Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroka Onishi Department of Immunobiology, Faculty of Pharmacy and Pharmaceutical Sciences, Okayama University Yuka Satoh Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Paul A. Roche Experimental Immunology Branch, National Cancer Institute, National Institutes of Health Satoshi Tanaka Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Kazuyuki Furuta Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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 Ca(2+)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 Ca(2+)mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs. No potential conflict of interest relevant to this article was reported.