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Investigation of functional hierarchy of antigen-specific T cells using comprehensive T cell receptor analysis technique

Research Project

Project/Area Number 16K19576
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionHiroshima University

Principal Investigator

Miyama Takahiko  広島大学, 病院(医), 医科診療医 (00770330)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsウイルス・腫瘍免疫 / T細胞受容体 / 次世代シークエンサー / シングルセルソーティング技術 / 免疫 / T細胞レセプター / ウイルス・癌抗原特異的T細胞 / 免疫学
Outline of Final Research Achievements

To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using a cytomegalovirus (CMV)-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals2017

    • Author(s)
      Miyama Takahiko、Kawase Takakazu、Kitaura Kazutaka、Chishaki Ren、Shibata Masashi、Oshima Kumi、Hamana Hiroshi、Kishi Hiroyuki、Muraguchi Atsushi、Kuzushima Kiyotaka、Saji Hiroh、Shin-I Tadasu、Suzuki Ryuji、Ichinohe Tatsuo
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 668-668

    • DOI

      10.1038/s41598-017-03855-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 次世代シーケンサー を用いた同種造血幹細胞移植後に残存する微小レシピエントT細胞クローンの解析2018

    • Author(s)
      美山貴彦
    • Organizer
      第40回日本造血細胞移植学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Landscape of immune reconstitution after allogeneic hematopoietic cell transplantation is superdominated by distinct T cell populations bearing T-cell receptor clonotypes shared among different individuals2017

    • Author(s)
      美山貴彦
    • Organizer
      第59回 米国血液学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TALEN-mediated T-cell receptor gene editing as a novel tool for adaptive T-cell immunotherapy2017

    • Author(s)
      美山貴彦
    • Organizer
      第79回 日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] サイトメガロウイルス反応性T細胞レパトワ形成に与える HLA-A*02の影響の次世代シーケンサーを用いた網羅的解析2016

    • Author(s)
      美山 貴彦
    • Organizer
      第25回日本組織適合性学会大会
    • Place of Presentation
      北海道大学学術交流会館
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Stem cell memory T-cells are a reservoir of functional T-cells highly shared among individuals2016

    • Author(s)
      美山 貴彦
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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