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Structural analysis of neo-self

Planned Research

Project AreaCreation, function and structure of neo-self
Project/Area Number 16H06500
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

YOKOYAMA Shigeyuki  国立研究開発法人理化学研究所, 科技ハブ産連本部, 特別招聘研究員 (00159229)

Co-Investigator(Kenkyū-buntansha) 笹月 健彦  九州大学, 高等研究院, 特別主幹教授 (50014121)
Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥207,740,000 (Direct Cost: ¥159,800,000、Indirect Cost: ¥47,940,000)
Fiscal Year 2020: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2019: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2018: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2017: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2016: ¥55,900,000 (Direct Cost: ¥43,000,000、Indirect Cost: ¥12,900,000)
Keywords免疫学 / タンパク質 / アレルギー・ぜんそく / 立体構造 / MHC / TCR / 蛋白質
Outline of Final Research Achievements

Based on the crystal structure of HLA-DP5 complexed with a 13-residue peptide (NF-pCj1) containing a 4-residue N-terminal flanking region (NF) derived from a cedar pollen antigen Cry j 1, the functionally-important hexameric structure of HLA-DP5 was elucidated, and it was clarified that this clustering significantly enhances TCR activation. Furthermore, the multimeric structure on the TCR side that binds to the hexameric structure of HLA-DP5 was clarified. Thus, it was concluded that the formation of this TCR multimeric structure is universal to the HLA-II・TCR complex leading to T cell activation, and is the structural entity on which “neo-self” is based.

Academic Significance and Societal Importance of the Research Achievements

従来は、T細胞活性化において、HLAおよびTCRのそれぞれが多量体化することの重要性は示唆されていたが、その直接的な検証と、立体構造的な実体は不明であった。本研究の成果として、「ネオ・セルフ」とは、TCRを強く活性化できる状態であり、その実体は「HLAとTCRの相互作用が、HLAの多量体とTCRの多量体との相互作用が可能になるペプチド提示様式」であると結論された。これにより、獲得免疫の中核である抗原提示の実体が解明されたことになり(学術的意義)、自己免疫疾患における抗原提示機構の理解に基づく治療、有効な感染症ワクチンやがんワクチンの設計・開発等に役立つと期待される(社会的意義)。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (8 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation.2018

    • Author(s)
      Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K, Azuma F, Yabe T, Satake M, Kato S, Kodera Y, Sasazuki T, Morishima Y
    • Journal Title

      Blood

      Volume: 131(7) Issue: 7 Pages: 808-817

    • DOI

      10.1182/blood-2017-08-801449

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Structure and function of an HLA-DP5 peptide complex2018

    • Author(s)
      Yokoyama Shigeyuki
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネオ・セルフの立体構造解析2017

    • Author(s)
      横山茂之
    • Organizer
      新学術領域研究「ネオ・セルフの生成・機能・構造」第1回領域全体班会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] The flanking region of cedar pollen peptide in complex with HLA-DP5 facilitates T-cell activation.2016

    • Author(s)
      Kusano, S., Ueda, S., Hamana, H., Kishi, H., Muraguchi, A., Ohsawa, N., Wakiyama, M., Yoshikai, Y., Yamada, H., Yamamoto, K., Kukimoto-niino, M., Nishimura, Y., Shirouzu, M., Sasazuki, T. and Yokoyama, S.
    • Organizer
      16th International Congress of Immunology (ICI2016)
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cls-lnteractlon of TCRs and antigen/MHC class 1 Complexes on CD8+ T cells causes their activation.2016

    • Author(s)
      Kishi, H., Jin, A., Hamana, H., Shitaoka, K., Tajiri, K., Kobayashi, E., Kusano, S., Yokoyama, S., Ozawa, T., Nagai, T., Obata, T., Hatakeyama, S., Horii, M., Hu, Y., Zhang, F. and Muraguchi, A.
    • Organizer
      16th International Congress of Immunology (ICI2016)
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] ネオ・セルフの生成・機能・構造

    • URL

      http://www.tokyo-med.ac.jp/neoself/index.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report

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Published: 2016-07-04   Modified: 2022-01-27  

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