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Generation mechanism of Neo-self by metal / chemical

Planned Research

Project AreaCreation, function and structure of neo-self
Project/Area Number 16H06497
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 InstitutionTohoku University

Principal Investigator

Kouetsu Ogasawara  東北大学, 加齢医学研究所, 教授 (30323603)

Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥90,870,000 (Direct Cost: ¥69,900,000、Indirect Cost: ¥20,970,000)
Fiscal Year 2020: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
KeywordsMHC / T細胞受容体 / ハプテン / 金属 / T細胞 / 抗原提示 / ネオ・セルフ / 免疫学 / アレルギー
Outline of Final Research Achievements

In this study, we investigated the molecular mechanism by which the antigen peptide-MHC complex modified by haptens as “neo-self”. To explore the mechanisms, we analyzed T cell receptors that react with haptens such as metal. We identified the metal allergy-specific T cell receptors in a mouse model of metal allergy using palladium (Pd). Furthermore, by in vitro cell culture system, we found that the antigen peptide-MHC complex was changed by Pd solution and the expression of MHC was transiently reduced. In other words, we found that the behavior of the antigen peptide-MHC complex induces changes in the repertoire of T cell receptors. Therefore, our findings suggest that the behavior of antigen peptide-MHC complex may be induce the neo-self.

Academic Significance and Societal Importance of the Research Achievements

本研究では、金属がハプテンとして機能するだけでなく、抗原ペプチド-MHC 複合体が パラジウム溶液によって変化し、MHC の発現が一過性に低下することを見出した。 つまり、抗原ペプチド-MHC複合体の挙動がT細胞受容体のレパートリーの変化を誘導した。我々の発見は、MHCの挙動を変化させることで、MHCが新たな自己抗原を認識する機構であるネオ・セルフという現象を示す結果を得た。すなわち、ネオ・セルフという概念の実証を示したという学術的意義を持つ。

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

    (23 results)

All 2021 2020 2019 2018 2017 2016

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 7 results,  Acknowledgement Compliant: 3 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer2021

    • Author(s)
      Inamori Koji、Togashi Yosuke、Fukuoka Shota、Akagi Kiwamu、Ogasawara Kouetsu、Irie Takuma、Motooka Daisuke、Kobayashi Yoichi、Sugiyama Daisuke、Kojima Motohiro、Shiiya Norihiko、Nakamura Shota、Maruyama Shoichi、Suzuki Yutaka、Ito Masaaki、Nishikawa Hiroyoshi
    • Journal Title

      JCI Insight

      Volume: 8 Issue: 9 Pages: 137365-137365

    • DOI

      10.1172/jci.insight.137365

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses2020

    • Author(s)
      Kosuge Masato、Furusawa-Nishii Emi、Ito Koyu、Saito Yoshiro、Ogasawara Kouetsu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17766-17766

    • DOI

      10.1038/s41598-020-74843-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] COX-2 induces T cell accumulation and IFN-γ production during the development of chromium allergy2019

    • Author(s)
      Sitalaksmi Ratri Maya、Ito Koyu、Ogasawara Kouetsu、Suto Yoshiko、Itabashi Madoka、Ueda Kyosuke、Hirasawa Noriyasu、Narushima Takayuki、Hendrijantini Nike、Kresnoadi Utari、Sasaki Keiichi
    • Journal Title

      Autoimmunity

      Volume: 52 Issue: 5-6 Pages: 228-234

    • DOI

      10.1080/08916934.2019.1662404

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 金属アレルギー研究の最前線2019

    • Author(s)
      小笠原康悦
    • Journal Title

      東北矯正歯科学会雑誌

      Volume: 26

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zinc ions have a potential to attenuate both Ni ion uptake and Ni ion-induced inflammation2018

    • Author(s)
      Onodera Ryo、Asakawa Sanki、Segawa Ryosuke、Mizuno Natsumi、Ogasawara Kouetsu、Hiratsuka Masahiro、Hirasawa Noriyasu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-018-21014-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nickel ions bind to HSP90β and enhance HIF-1α-mediated IL-8 expression2018

    • Author(s)
      Asakawa S, Onodera R, Kasai K, Kishimoto Y, Sato T, Segawa R, Mizuno N, Ogasawara K, Moriya T, Hiratsuka M, Hirasawa N
    • Journal Title

      Toxicology

      Volume: 395 Pages: 45-53

    • DOI

      10.1016/j.tox.2018.01.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy2017

    • Author(s)
      Takeda Yuri、Suto Yoshiko、Ito Koyu、Hashimoto Wataru、Nishiya Tadashi、Ueda Kyosuke、Narushima Takayuki、Takahashi Tetsu、Ogasawara Kouetsu
    • Journal Title

      Int J Mol Sci.

      Volume: 18 Issue: 6 Pages: 1162-1162

    • DOI

      10.3390/ijms18061162

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro evaluation of Ag-containing calcium phosphates: Effectiveness of Ag-incorporated β-tricalcium phosphate2017

    • Author(s)
      O. Gokcekaya, K. Ueda, K. Ogasawara, H. Kanetaka, T. Narushima
    • Journal Title

      Mater. Sci. Eng. C

      Volume: 75 Pages: 926-933

    • DOI

      10.1016/j.msec.2017.02.059

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The potential role of Osteopontin in the maintenance of commensal bacteria homeostasis in the intestine.2017

    • Author(s)
      Ito K, Nakajima A1, Fukushima Y1, Suzuki K1, Sakamoto K, Hamazaki Y, Ogasawara K, Minato N, and Hattori M.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 3 Pages: e0173629-e0173629

    • DOI

      10.1371/journal.pone.0173629

    • NAID

      120006488574

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cytotoxicity of natural killer cells activated through NKG2D contributes to the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model.2017

    • Author(s)
      Kawakami T, Ito K, Matsuda Y, Noda M, Sakurada A, Hoshikawa Y, Okada Y, Ogasawara K.
    • Journal Title

      Am J Transplant.

      Volume: 印刷中 Issue: 9 Pages: 2338-2349

    • DOI

      10.1111/ajt.14257

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting.2017

    • Author(s)
      Takeda K, Nakayama M, Hayakawa Y, Kojima Y, Ikeda H, Imai N, Ogasawara K, Okumura K, Thomas DM, Smyth MJ
    • Journal Title

      Nat Commun.

      Volume: 8 Issue: 1 Pages: 14607-14607

    • DOI

      10.1038/ncomms14607

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] マウスモデルを用いた歯科金属アレルギーの分子機構2017

    • Author(s)
      小笠原康悦
    • Journal Title

      炎症と免疫

      Volume: 25 Pages: 11-16

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 金属と炎症2017

    • Author(s)
      小笠原康悦
    • Journal Title

      炎症と免疫

      Volume: 25 Pages: 1-3

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Quantitative in vivo biocompatibility of new ultralow-nickel cobalt-chromium-molybdenum alloys2016

    • Author(s)
      Yoshihiro Hagiwara, Kazuaki Sonofuchi, Yuichiro Koizumi, Akihiko Chiba, Mitsuko Kawano, Masafumi Nakayama, Kouetsu Ogasawara, Eiji Itoi
    • Journal Title

      Journal of Orthopaedic Research

      Volume: in press Issue: 9 Pages: 1505-1513

    • DOI

      10.1002/jor.23150

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 金属アレルギー研究の最前線2018

    • Author(s)
      小笠原康悦
    • Organizer
      東北矯正歯科学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] TRAV7-2*02-expressing CD8+ T cells are responsible for Palladium allergy2018

    • Author(s)
      Yuri Takeda, Kouetsu Ogasawara, Tetsu Takahashi
    • Organizer
      The 57th Congress of Korean Association of Maxillofacial Plastic and Reconstructive Surgeons
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of the pathogenic T cells in metal allergy2018

    • Author(s)
      Kouetsu Ogasawara
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis on metal-responsive T cells in Palladium Allergy2018

    • Author(s)
      Koyu ITO, Yuri Takeda, Yoshiko Suto, Madoka Itabashi, Kouetsu Ogasawara
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NbとAgを添加した非晶質リン酸カルシウム膜の溶解性と 抗菌性2018

    • Author(s)
      上田 恭介 、井上 紅花 、伊藤 甲雄、 小笠原 康悦 、成島 尚之
    • Organizer
      公益社団法人 日本金属学会 2018年春期(第162回)講演大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 金属アレルギーを引き起こすT細胞の特定2017

    • Author(s)
      武田裕利、須藤佳子、佐藤直毅、樋口繁仁、高橋哲、伊藤甲雄、小笠原康悦
    • Organizer
      第71回 日本細菌学会東北支部総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Antibacterial property of visible-light active TiO2 layers formed on Ti-Au alloys by thermal oxidation2017

    • Author(s)
      Takatoshi Ueda, Shota Sado, Kyosuke Ueda, Koyu Ito, Kouetsu Ogasawara, Takayuki Mokudai, Hiroyasu Kanetaka, Yoshimi Niwano, Takayuki Narushima
    • Organizer
      28th European Conference on Biomaterials, Athens, Greece
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ag 含有リン酸カルシウム焼結体の溶解性および抗菌性評価2017

    • Author(s)
      上田 恭介,Ozkan GOKCEKAYA,伊藤 甲雄,小笠原 康悦,金髙 弘恭,中野 貴由,成島 尚之
    • Organizer
      一般社団法人 粉体粉末冶金協会. 平 成 29 年 度 秋 季 大 会. (第120回講演大会)
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] Gene-specific unbiased amplification method2017

    • Inventor(s)
      Ogasawara K
    • Industrial Property Rights Holder
      Ogasawara K
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas

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

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