Intracellular trafficking mechanisms regulating the level of antigen presentation in dendritic cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Okayama University
• Principal Investigator: Furuta Kazuyuki 岡山大学, 医歯薬学総合研究科, 准教授 (50644936)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 樹状細胞 / MHC-II / エンドサイトーシス

Outline of Final Research Achievements

Dendritic cells induce an immune response by presenting pathogen-derived antigens to T cells by major histocompatibility antigen class II (MHC-II). The cell surface expression level of MHC-II is a regulator of the immune response. We have previously found that crosslinking of MHC-II by the TCR of activated T cells induces endocytosis of MHC-II. In this study, we analyzed the signaling mechanism induced by MHC-II crosslinking. We found that crosslinking of MHC-II induces calcium influx via activation of Syk/PLC, resulting in clathrin-dependent endocytosis of MHC-II mediated with PKC activation.

Free Research Field

生化学・細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、MHC-IIの細胞表面からのダウンレギュレーション機構として、カルシウム流入によるPKCの活性化を介した、クラスリン依存的エンドサイトーシスという新たなMHC-IIのエンドサイトーシスを誘導する機構が明らかとなった。今後、MHC-IIの発現異常の関連する疾患において、MHC-IIの発現調節の標的となる可能性が考えられる。