• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification of endoplasmic reticulum molecular chaperones to determine antigen presentation to cytotoxic T lymphocytes

Research Project

Project/Area Number 18K06631
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionSaitama Medical University

Principal Investigator

Matsui Masanori  埼玉医科大学, 医学部, 准教授 (50199741)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords細胞傷害性T細胞 / HLAクラスI / 抗原提示 / 分子シャペロン / 小胞体 / アジュバント / TAPBPR / SARS-CoV-2
Outline of Final Research Achievements

The HLA-A2 mutant molecule HLA-A2-H74L with one amino acid substitution from Histidine to Leucine at position 74 fails to present antigen to cytotoxic T cells because it does not bind to endogenously processed antigenic peptides. This phenomenon is thought to be due to the lack of the interaction between HLA-A2-H74L and an unknown molecular chaperone in the ER, which may assist to exchange from self-peptides to antigenic peptides.
We attempted to identify this molecule using immunoprecipitation and mass spectrometry, but we failed. At that time, a new molecular chaperone, TABPPR, was identified. Due to its properties, it is highly possible that the molecular chaperone in question is TABPPR. The analysis of a human cell line in which TABPPR was knocked out by the CRISPR/Cas9 method revealed the antigen-presenting ability of the cell line was slightly reduced, suggesting a critical role of TAPBPR in the antigen presentation associated with HLA class I.

Academic Significance and Societal Importance of the Research Achievements

細胞傷害性T細胞 (CTL)は、がん細胞やウイルス感染細胞の排除に極めて重要な役割を果たしている。従って、その誘導を行う抗原提示機構を理解する事は重要である。本研究では、新規小胞体分子シャペロン、TAPBPRの抗原提示における重要性が示唆された。この分子シャペロンは抗原提示能を促進すると考えられるので、がんやウイルス感染症に対する新しいCTL誘導型ワクチンに利用できるであろう。さらに、治療薬・治療法の標的分子となりえる。このように、本研究結果は学術的に高い意味を持つとともに、ワクチンなど臨床応用も期待でき、社会的に大きな意義を持つと思われる。

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

    (11 results)

All 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (4 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Identification of HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2 and analysis of their conservation using the mutation database of SARS-CoV-2 variants.2021

    • Author(s)
      Takagi A., and M. Matsui
    • Journal Title

      Microbiology Spectrum

      Volume: 9 Issue: 3

    • DOI

      10.1128/spectrum.01659-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of HLA-A*02:01-Restricted Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 That May Be Natural Targets of CD8+ T Cell Recognition In Vivo2021

    • Author(s)
      Takagi Akira、Matsui Masanori
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 5

    • DOI

      10.1128/jvi.01837-20

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 402020

    • Author(s)
      Saika Kikue、Kato Masahiko、Sanada Hideaki、Matsushita Sho、Matsui Masanori、Handa Hiroshi、Kawano Masaaki
    • Journal Title

      Journal of General Virology

      Volume: 101 Issue: 8 Pages: 853-862

    • DOI

      10.1099/jgv.0.001445

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tannic acid acts as an agonist of the dopamine D2L receptor, regulates immune responses, and ameliorates experimentally induced colitis in mice2020

    • Author(s)
      Kawano Masaaki、Saika Kikue、Takagi Rie、Matsui Masanori、Matsushita Sho
    • Journal Title

      Brain, Behavior, & Immunity - Health

      Volume: 5 Pages: 100071-100071

    • DOI

      10.1016/j.bbih.2020.100071

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dopamine regulates cytokine secretion during innate and adaptive immune responses.2019

    • Author(s)
      Kawano, M., Takagi, R., Saika, K., Matsui, M., Matsushita, S.
    • Journal Title

      International Immunology

      Volume: 30 Issue: 12 Pages: 591-606

    • DOI

      10.1093/intimm/dxy057

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 新型コロナウイルス由来CTLエピトープの同定とCTL誘導型ワクチン応用への可能性2020

    • Author(s)
      松井政則、高木徹
    • Organizer
      BioJapan 2020
    • Related Report
      2020 Research-status Report
  • [Presentation] 抗原提示に関連した分子シャペロンの同定に必要な新規CTL assayの確立2019

    • Author(s)
      高木徹、村上孝、松井政則
    • Organizer
      埼玉医大 第17回 RCGM フロンディアシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 分子シャペロンgp96の抗原提示に関する研究2018

    • Author(s)
      高木徹、松井政則
    • Organizer
      第22回日本ワクチン学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Tannic acid affects dopamine receptors, regulates immune responses, and ameliorates experimentally induced colitis.2018

    • Author(s)
      Kawano, M., Saika, K., Takagi, R., Matsui, M., Matsushita, S.
    • Organizer
      第76回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Book] Magnetic Nanoparticles for Medical Diagnostics2018

    • Author(s)
      Kawano, M., Hatakeyama, M., Matsui, M., Handa, H.
    • Total Pages
      29
    • Publisher
      IOP-SCIENCE
    • ISBN
      9780750315845
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] SARS-CoV-2の細胞傷害性T細胞エピトープペプチド及びその利用2020

    • Inventor(s)
      松井政則、高木徹
    • Industrial Property Rights Holder
      松井政則、高木徹
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-120675
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi