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Understanding of cellular ligand discrimination as a stochastic information processing system and its application for the control of immunological self/non-self discrimination

Research Project

Project/Area Number 18K18147
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionUniversity of Fukui (2019-2021)
The University of Tokyo (2018)

Principal Investigator

Kajita Masashi  福井大学, 学術研究院工学系部門, 助教 (40804191)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsシステム生物学 / 数理生物学 / 確率モデル / 化学反応ネットワーク / T細胞 / 分子認識 / 分子識別 / 理論免疫学 / 数理モデル / 抗原識別 / ノイズ / 免疫 / 免疫学
Outline of Final Research Achievements

Immune T cells recognize antigenic peptides using receptor molecules on the cell surface, and discriminate between target and non-target ligands even though the difference is only a single amino acid substitution. This ligand recognition is conducted by a reaction system composed of a relatively small number of receptor molecules. However, little is known about the mechanism for accurate ligand discrimination under the stochastic noise due to the small number effect. In this study, we mathematically modeled and analyzed immune T cells' antigen recognition reaction systems. We clarified the reaction network structure that non-linearly amplifies the difference between the target and non-target ligands by utilizing noise. We also analyzed parameters that can control ligand discrimination accuracy and threshold of target and non-target ligands.

Academic Significance and Societal Importance of the Research Achievements

免疫T細胞は類似する非標的分子が多数混在するなかで、標的分子を正確に識別している。さらに抗原識別反応は比較的少数の分子からなる確率的な反応系で構成されており、確率ノイズ下で正確な分子識別を可能にするメカニズムは不明である。本研究ではT細胞抗原認識過程を数理モデル化し、T細胞が直感に反してノイズと混在する非標的分子を活用して識別精度を高めるメカニズムがありうることを理論的に明らかにした。さらに上記以外のT細胞抗原識別モデルの構築と解析についても広く行なった。本成果はT細胞を利用した治療法開発における理論的土台に発展することが期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] An Error Correction Mechanism for Reliable Chemical Communication Systems2020

    • Author(s)
      Kajita Masashi K.
    • Journal Title

      Journal of Robotics, Networking and Artificial Life

      Volume: 7 Issue: 1 Pages: 52-52

    • DOI

      10.2991/jrnal.k.200512.011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reliable target ligand detection by noise-induced receptor cluster formation2020

    • Author(s)
      Kajita Masashi K.、Aihara Kazuyuki、Kobayashi Tetsuya J.
    • Journal Title

      Chaos: An Interdisciplinary Journal of Nonlinear Science

      Volume: 30 Issue: 1 Pages: 011104-011104

    • DOI

      10.1063/1.5140714

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative biology of ligand discrimination by immune T cells2019

    • Author(s)
      梶田 真司
    • Journal Title

      SEISAN KENKYU

      Volume: 71 Issue: 2 Pages: 125-132

    • DOI

      10.11188/seisankenkyu.71.125

    • NAID

      130007627749

    • ISSN
      0037-105X, 1881-2058
    • Year and Date
      2019-03-01
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞内局在変化が生み出す免疫・神経機能への数理的アプローチ2021

    • Author(s)
      梶田 真司
    • Organizer
      合原・村上ムーンショット Projects 合同ワークショップ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 免疫T細胞が類似抗原を識別するメカニズムについての理論的考察2020

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      第4回理論免疫学ワークショップ
    • Related Report
      2019 Research-status Report
  • [Presentation] An error correction mechanism for reliable chemical communication systems2020

    • Author(s)
      Masashi K. Kajita
    • Organizer
      The 2020 International Conference on Artificial Life and Robotics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫T細胞による抗原識別現象の理解に向けた数理モデリング2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      第一回 データ駆動数理医科学ワークショップ
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 免疫 T 細胞の抗原識別における確率ノイズの機能2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      2019年度 日本数理生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Stochastic mechanism on cellular ligand discrimination2019

    • Author(s)
      Kajita Masashi K.、Aihara Kazuyuki、Kobayashi Tetsuya J.
    • Organizer
      2nd JOINT SYMPOSIUM BETWEEN MECHANOBIOLOGY INSTITUTE, National University of Singapore AND UNIVERSAL BIOLOGY INSTITUTE, The University of Tokyo, Japan
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of stochastic noise in ligand discrimination2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 確率ノイズを活用した細胞内エラー訂正機構2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      「細胞を創る」研究会12.0
    • Related Report
      2019 Research-status Report
  • [Presentation] 多様な分子を識別する細胞内反応系における空間効果の理解に向けて2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      定量生物学の会 北海道キャラバン2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫学的自己/非自己識別現象の理解に向けた理論的取り組み2019

    • Author(s)
      梶田真司、合原一幸、小林徹也
    • Organizer
      人間行動科学研究拠点公開講義 人間研究のための基礎知識
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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