Toward a new understanding of acquired immune system via structural analysis of MHC-crossreative T cells
| 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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Report
(3 results)
Research Products
(18 results)
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[Presentation] Longitudinal analysis of B cell repertoire after allogeneic HCT by comprehensive immunosequencing.2020
Author(s)
Ichinohe T, Kawase T, Fujino K, Edahiro T, Toishigawa K, Mino T, Yoshida T, Nagoshi H, Fukushima N, Nakamura Y, Kitaura K, Shin-I T, Suzuki R, Homan JE, Bremel RD.
Organizer
第42回日本造血細胞移植学会総会.
Related Report
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[Presentation] TALENによるゲノム編集技術を用いた内在性TCR遺伝子のノックアウト及び目的遺伝子の導入.2020
Author(s)
長谷川志穂, 川瀬孝和 , 吉田奈央, 小林美咲, 田辺季佐, 本庶仁子, 土石川佳世, 美山貴彦, 佐藤寛之, 鈴木隆二, 佐久間哲史, 山本 卓, 一戸辰夫.
Organizer
第42回日本造血細胞移植学会総会.
Related Report
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[Presentation] Comprehensive T cell receptor (TCR) repertoire analysis of new T cell subsets with naive phenotype.2018
Author(s)
Kisa Tanabe, Takakazu Kawase, Kazutaka Kitaura, Takahiko Miyama, Misaki Kobayashi, Mayu Sato, Takayuki Oda, Aoi Sakamoto, Kiyoto Tanaka, Kiyotaka Kuzushima, Kazuo Yamashita, Tadasu Shin-I, Ryuji Suzuki, Tatsuo Ichinohe.
Organizer
第80回日本血液学会学術集会
Related Report
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