2022 Fiscal Year Final Research Report
From treatment to prevention: development of innovative immune regulation based on epitope/paratope analysis
Project/Area Number |
20H03818
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 56030:Urology-related
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Research Institution | Aichi Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
岩崎 研太 愛知医科大学, 医学部, 准教授 (10508881)
三輪 祐子 愛知医科大学, 医学部, 助教 (90572941)
野田 貴幸 愛知医科大学, 災害医療研究センター, 薬剤師 (50817088)
石山 宏平 愛知医科大学, 医学部, 准教授 (50437589)
勝野 敬之 愛知医科大学, 医学部, 教授 (60642337)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 移植・再生医療 / 腎移植 / 免疫制御 / エピトープ / パラトープ / 慢性抗体関連型拒絶反応 / ウイルス感染 |
Outline of Final Research Achievements |
Further improvement of long-term outcomes is an important issue in renal transplantation. Obstacles are chronic rejection due to antibodies against donor HLA (DSA) and infections caused by excessive immunosuppressive therapy. We have developed an understanding of epitopes and paratopes (i.e., T-cell receptors: TCR) with the aim of suppressing DSA production while maintaining and promoting immune response against the virus. The significance of T-cell and B-cell epitope matching for DSA production in clinical renal transplantation was clarified, allowing for optimization of maintenance immunosuppressive therapy. Risk factors for BK virus (BKV) infection, for which there is no effective therapy, were identified, and T-cell immune response monitoring was developed. Single cell RNA analysis was performed to identify TCRs that recognize these epitopes, and a pathway from treatment to prevention would be established.
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Free Research Field |
腎移植、移植免疫
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Academic Significance and Societal Importance of the Research Achievements |
現状の免疫抑制療法では、ウイルスの免疫応答を維持・促進しながら、ドナーに対する免疫応答(ドナーHLAに対する抗体産生)を抑制することは困難である。特定のエピトープ、T細胞受容体を同定し、ターゲットとなる免疫応答を促進・抑制する超選択的な免疫制御法の開発に取り組んだ。エピトープ解析の意義を明確にし、免疫抑制適正化を可能とした。 また、ウイルス、ドナーに対するT細胞受容体解析により治療、予防を行う戦略が明確になった。得られた知見は臓器のみならず造血幹細胞移植、がんペプチドワクチン、感染症全般にも広がる可能性がある。
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