Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II

• Main Authors: Kento Masaki, Yuhji Hiraki, Hiroka Onishi, Yuka Satoh, Paul A. Roche, Satoshi Tanaka, Kazuyuki Furuta
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Cells
• Subjects: MHC-II; dendritic cells; endocytosis; crosslink; PKC
• Online Access: https://www.mdpi.com/2073-4409/9/8/1810

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.