Artificial control technology of antigen presentation by regulation of MHC expression

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19415
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Hatakeyama Shigetsugu 北海道大学, 医学研究院, 教授 (70294973)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: ユビキチン / MHC

Outline of Final Research Achievements

The ubiquitin-proteasome system and autophagy are intracellular protein degradation systems important for the production of antigenic proteins. Many intracellular proteins are degraded by the ubiquitin-proteasome system and presented as antigenic peptides on MHC class I via the endoplasmic reticulum. In addition, peptide antigens which are degraded by the autophagy system enter the endoplasmic reticulum, and are presented on MHC class II. In this application, we proceeded to elucidate the regulation of antigen presentation by E3 ubiquitin ligases, focusing on TRIM-type ubiquitin ligases involved in autophagy and antigen presentation.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

免疫疾患の発症において、免疫細胞のセレクション過程に異常も想定されるが、抗原側の質的及び量的な異常が、免疫細胞を活性化し疾患が発症することも推定される。さらに、生体の免疫反応では「affinity」だけでなく「avidity（affinityの総和）」も重要であり、「抗原の質」だけでなく、「抗原の量」の変化も免疫反応を左右すると考えられる。本研究はMHC発現制御に関する遺伝子の探索的意味合いがある。今後、本研究の成果は、新規の免疫反応の調節剤開発（自己免疫疾患、アレルギー性疾患、炎症性疾患、感染症等）のための知見を提供する可能性がある。