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Regulation of negative selection by fine-tuning TCR responsiveness through positive selection

Research Project

Project/Area Number 17K15727
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

KONDO Kenta  徳島大学, 先端酵素学研究所(プロテオ), 専門研究員 (60779974)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胸腺 / T細胞 / 正の選択 / 負の選択 / 免疫学 / 獲得免疫 / T細胞選択
Outline of Final Research Achievements

Cortical thymic epithelial cells (cTECs) present self-peptide-MHC complexes to DP thymocytes for positive selection. cTECs specifically express thymoproteasomes which produce unique self-peptides for promoting generation of CD8+ T cells. it is unclear how thymoproteasome-dependent positive selection affects negative selection in thymic medulla and TCR repertoire formation. We found that thymoproteasome-dependent positive selection produces unique TCRs in CD8+ T cells.

Academic Significance and Societal Importance of the Research Achievements

CD8+ T細胞は、様々な抗原を認識可能なTCRレパートリーを形成することで生体防御に寄与する。正の選択を司る胸腺皮質上皮細胞で特異的に発現する胸腺プロテアソームを欠損するマウスでは著しくCD8+ T細胞が減少することから、胸腺プロテアソームはCD8+ T細胞のTCRレパートリー形成に寄与すると考えられている。しかし、胸腺プロテアソームがどのようにTCRレパートリー形成するのかについては明らかではない。
本研究により、胸腺プロテアソームが形成するTCRレパートリーを明らかにすることで、感染症や悪性腫瘍に対する免疫応答の更なる理解に繋がることが予想される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Thymus machinery for T-cell selection2019

    • Author(s)
      Kondo K, Ohigashi I, Takahama Y
    • Journal Title

      International Immunology

      Volume: 31 Issue: 3 Pages: 119-125

    • DOI

      10.1093/intimm/dxy081

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity2018

    • Author(s)
      Morimoto Soyoko、Fujiki Fumihiro、Kondo Kenta、Nakajima Hiroko、Kobayashi Yoshiki、Inatome Miki、Aoyama Nao、Nishida Yuya、Tsuboi Akihiro、Oka Yoshihiro、Nishida Sumiyuki、Nakata Jun、Hosen Naoki、Oji Yusuke、Sugiyama Haruo
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 75 Pages: 34132-34141

    • DOI

      10.18632/oncotarget.26139

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antigen processing and presentation in the thymus: implications for T cell repertoire selection2017

    • Author(s)
      Kondo Kenta、Takada Kensuke、Takahama Yousuke
    • Journal Title

      Current Opinion in Immunology

      Volume: 46 Pages: 53-57

    • DOI

      10.1016/j.coi.2017.03.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Thymoproteasome-dependent positive selection conditions in vivo immune responses in CD8+ T cells2017

    • Author(s)
      Kenta Kondo, Kensuke Takada, Yousuke Takahama
    • Organizer
      日本免疫学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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