| Project/Area Number |
18K19452
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Hiroshima University |
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Principal Investigator |
ICHINOHE TATSUO 広島大学, 原爆放射線医科学研究所, 教授 (80314219)
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| Co-Investigator(Kenkyū-buntansha) |
本庶 仁子 広島大学, 原爆放射線医科学研究所, 講師 (80614106)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | T細胞受容体 / 立体構造 / 交差反応性 / 免疫シーケンシング / シングルセルゲノミクス / 主要組織適合性抗原複合体 / 網羅的免疫シークエンス / 共有クロノタイプ |
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| Outline of Final Research Achievements |
In this study, we accumulated approximately 2.3 million T-cell receptor (TCR) beta chain clonotypes from peripheral blood in recipients of allogeneic hematopoietic cell transplantation (HCT). Of these clonotypes, 42,436 (1.5%) were proven to be shared between different recipients. Notably, whole T-cell repertoires of post-HCT recipients were predominated by “shared TCR clonotypes” irrespective of donor-recipient HLA compatibility. As a good example, we also identified two HLA-B7-restricted CMV-reactive TCR clonotypes in the TCR repertoire of HLA-B7-negative recipients. Additionally for in toto analysis of T-cell reconstitution at the individual level, we have created an MHC-partially mismatched zebrafish HCT model and found that predominant TCR clonotypes in post-transplant recipients were substantially different from those in donor graft.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を通じて得られた知見は、「共有TCR」がMHC交差的(crossreactive)に免疫学的優位性を保有する可能性を示唆するものであり、「単一レセプター単一抗原」に代わる獲得免疫系の新たな理解への道を開くものとして、学術的に重要な意義を有する。また、本研究で開発を行ったTCR遺伝子導入用の非ウイルスベクターはわが国独自の技術による遺伝子改変T細胞医薬品の開発に貢献し得る。
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