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ネオセルフ化ペプチドによる新規免疫制御機構の解明

Publicly Offered Research

Project AreaCreation, function and structure of neo-self
Project/Area Number 17H05793
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 InstitutionOsaka University

Principal Investigator

荒瀬 尚  大阪大学, 微生物病研究所, 教授 (10261900)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsネオセルフ / MHC / T細胞 / 抗体
Outline of Annual Research Achievements

MHCクラスII分子は、ペプチドをヘルパーT細胞に提示することで、免疫応答の中心的な役割を担っている。我々はMHCクラスII分子に提示されたミスフォールド蛋白質が自己抗体の標的であり、MHCクラスII分子はB細胞に対する抗原を提示し、抗体産生に関与することを明らかにしてきた。一方、T細胞レセプターと同様にペプチド・MHCクラスII分子複合体を認識するモノクローナル抗体が知られており、それらは、MHCによる抗原提示機構の解析のツールとして使われてきた。一方、我々は特定の抗原やペプチドに対する免疫応答では、ペプチド/MHCクラスII分子複合体に対する抗体が産生されることを発見した。そこで、本研究では、抗ペプチド/MHCクラスII分子複合体抗体の産生機序を解明し、抗ペプチド/MHCクラスII分子複合体抗体の機能を解明を目的とした。本研究では、抗ペプチド/MHCクラスII分子複合体抗体を誘導するネオ・セルフ化ペプチド配列に関して蛋白質抗原のペプチドライブリーを用いて解析した結果、ペプチド/MHCクラスII複合体抗体を誘導するネオセルフ化ペプチドの配列が存在することが明らかになった。さらに、これらのペプチド/MHCクラスII複合体に対する機能を解析したところ、抗原特異的にT細胞の認識を阻害することが明らかになった。さらに、EAE等の自己免疫疾患モデルマウスにペプチドを投与して抗ペプチド/MHCクラスII分子複合体抗体を誘導することによって、疾患発症を抑制できることが明らかになった。したがって、抗ペプチド/MHCクラスII複合体抗体を誘導することによって、免疫応答を抗原特異的に制御できる可能性が明らかになった。今後、さらに、抗ペプチド/MHCクラスII複合体抗体の機能と産生機構を解明することが、抗原特異的な免疫制御法の開発に重要であると考えられる。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (53 results)

All 2019 2018 2017 Other

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (36 results) (of which Int'l Joint Research: 7 results,  Invited: 18 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Transport of cellular misfolded proteins to the cell surface by HLA-B27 free heavy chain.2019

    • Author(s)
      Yorifuji H, Arase N, Kohyama M, Hirano T, Suenaga T, Kumanogoh A, Arase H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 511 Issue: 4 Pages: 862-868

    • DOI

      10.1016/j.bbrc.2019.02.120

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FcγRIIIA-mediated activation of NK cells by IgG heavy chain complexed with MHC class II molecules.2019

    • Author(s)
      Shimizu Y, Kohyama M, Yorifuji H, Jin H, Arase N, Suenaga T, Arase H.
    • Journal Title

      Int Immunol.

      Volume: Epub ahead of print Issue: 5 Pages: 303-314

    • DOI

      10.1093/intimm/dxz010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Invariant chain p41 mediates production of soluble MHC class II molecules.2019

    • Author(s)
      Shishido T, Kohyama M, Nakai W, Matsumoto M, Miyata H, Suenaga T, Arase H.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 509 Issue: 1 Pages: 216-221

    • DOI

      10.1016/j.bbrc.2018.12.106

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity.2018

    • Author(s)
      Chen HM, van der Touw W, Wang YS, Kang K, Mai S, Zhang J, Alsina-Beauchamp D, Duty JA, Mungamuri SK, Zhang B, Moran T, Flavell R, Aaronson S, Hu HM, Arase H, Ramanathan S, Flores R, Pan PY, Chen SH.
    • Journal Title

      J. Clin. Invest.

      Volume: 128 Issue: 12 Pages: 5647-5662

    • DOI

      10.1172/jci97570

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.2018

    • Author(s)
      Deng M, 外30名, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, Zhang CC.
    • Journal Title

      Nature.

      Volume: 562 Issue: 7728 Pages: 605-609

    • DOI

      10.1038/s41586-018-0615-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.2018

    • Author(s)
      Kayama H, Kohyama M, Okuzaki D, Motooka D, Barman S, Okumura R, Muneta M, Hoshino K, Sasaki I, Ise W, Matsuno H, Nishimura J, Kurosaki T, Nakamura S, Arase H, Kaisho T, Takeda K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 115 Issue: 33 Pages: 8418-8423

    • DOI

      10.1073/pnas.1808426115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MHCクラスⅡ分子のミスフォールドタンパク質の提示による自己抗体産生2018

    • Author(s)
      宍戸達也、荒瀬 尚
    • Journal Title

      炎症と免疫

      Volume: 26 Pages: 478-483

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors2017

    • Author(s)
      Saito Fumiji、Hirayasu Kouyuki、Satoh Takeshi、Wang Christian W.、Lusingu John、Arimori Takao、Shida Kyoko、Palacpac Nirianne Marie Q.、Itagaki Sawako、Iwanaga Shiroh、Takashima Eizo、Tsuboi Takafumi、Kohyama Masako、Suenaga Tadahiro、Colonna Marco、Takagi Junichi、Lavstsen Thomas、Horii Toshihiro、Arase Hisashi
    • Journal Title

      Nature.

      Volume: 552 Issue: 7683 Pages: 101-105

    • DOI

      10.1038/nature24994

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILRα immune cell receptor2017

    • Author(s)
      Furukawa Atsushi、Kakita Kosuke、Yamada Tomoki、Ishizuka Mikihiro、Sakamoto Jiro、Hatori Nanao、Maeda Naoyoshi、Ohsaka Fumina、Saitoh Takashi、Nomura Takao、Kuroki Kimiko、Nambu Hisanori、Arase Hisashi、Matsunaga Shigeki、Anada Masahiro、Ose Toyoyuki、Hashimoto Shunichi、Maenaka Katsumi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 51 Pages: 21128-21136

    • DOI

      10.1074/jbc.m117.799239

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells2017

    • Author(s)
      Dai Hong-Sheng、Griffin Nathaniel、Bolyard Chelsea、Mao Hsiaoyin Charlene、Zhang Jianying、Cripe Timothy P.、Suenaga Tadahiro、Arase Hisashi、Nakano Ichiro、Chiocca E.A.、Kaur Balveen、Yu Jianhua、Caligiuri Michael A.
    • Journal Title

      Immunity

      Volume: 47 Issue: 1 Pages: 159-170.e10

    • DOI

      10.1016/j.immuni.2017.06.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel autoantibody against the β2-glycoprotein I/HLA-DR complex in patients with refractory cutaneous ulcers2017

    • Author(s)
      Arase N, Tanimura K, Jin H, Yamaoka T, Kishibe M, Nishioka M, Kiyohara E, Tani M, Matsuoka S, Ohmura K, Takasugi K, Yamamoto T, Murota H, Arase H, Katayama I.
    • Journal Title

      Br J Dermatol.

      Volume: 印刷中 Issue: 1 Pages: 272-275

    • DOI

      10.1111/bjd.15571

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Myeloperoxidase/HLA Class II Complexes Recognized by Autoantibodies in Microscopic Polyangiitis2017

    • Author(s)
      Hiwa Ryosuke、Ohmura Koichiro、Arase Noriko、Jin Hui、Hirayasu Kouyuki、Kohyama Masako、Suenaga Tadahiro、Saito Fumiji、Terao Chikashi、Atsumi Tatsuya、Iwatani Hirotsugu、Mimori Tsuneyo、Arase Hisashi
    • Journal Title

      Arthritis Rheumatol.

      Volume: 69 Issue: 10 Pages: 2069-2080

    • DOI

      10.1002/art.40170

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 自己抗体の新たな標的分子:ネオ・セルフ2017

    • Author(s)
      末永忠広、 荒瀬 尚
    • Journal Title

      リウマチ科

      Volume: 58 Pages: 326-333

    • Related Report
      2017 Annual Research Report
  • [Journal Article] MHCクラス II の再発見ーネオ・セルフ:ミスフォールドタンパク質/MHCクラスⅡ分子複合体による新たな自己免疫疾患発症機構ー2017

    • Author(s)
      辻 英輝、荒瀬 尚
    • Journal Title

      The LUNG

      Volume: 25 Pages: 61-65

    • Related Report
      2017 Annual Research Report
  • [Presentation] ネオ・セルフによる新たな自己免疫疾患発症機構2019

    • Author(s)
      荒瀬 尚
    • Organizer
      第5回免疫セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] T細胞レセプターと同様な抗原特異性を示す抗体による新たな免疫制御機構2018

    • Author(s)
      岸田 一輝, 香山雅子, 末永忠広, 荒瀬 尚
    • Organizer
      第28 回Kyoto T cell Conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] ネオセルフによる新たな免疫疾患発症機構2018

    • Author(s)
      荒瀬 尚
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] MHCクラスⅡ分子を標的とした免疫疾患の新たな診断法、治療法の開発2018

    • Author(s)
      荒瀬 尚
    • Organizer
      第3回 バイオ医薬EXPO
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ペア型レセプターを介した宿主病原体相互作用2018

    • Author(s)
      荒瀬 尚
    • Organizer
      第17回四国免疫フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Immune evasion by pathogens via MHC class I recognizing inhibitory receptors2018

    • Author(s)
      Hisashi Arase
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Paired LILR family receptors in host pathogen interactions2018

    • Author(s)
      Hisashi Arase
    • Organizer
      ECI 2018(The 5th European Congress of Immunology)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Host Molecules Associating with Human Herpesvirus 6(HHV-62018

    • Author(s)
      Yuriko Muramatsu, Tadahiro Suenaga, Masako Kohyama, Hisashi Arase
    • Organizer
      第17回あわじしま感染症・免疫フォーラム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Paired receptors in host-pathogen interaction2018

    • Author(s)
      Hisashi Arase
    • Organizer
      Japanese-German Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HLAシャペロン様機能を介した新たな自己免疫疾患発症機構2018

    • Author(s)
      荒瀬 尚
    • Organizer
      第45回愛媛リウマチ研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] T細胞レセプターと同様な抗原特異性を示す抗体による新たな免疫制御機構2018

    • Author(s)
      岸田 一輝, 荒瀬 尚
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗リン脂質抗体症候群における抗β2GPI/HLAクラスII複合体抗体2018

    • Author(s)
      荒瀬 尚
    • Organizer
      日本抗リン脂質抗体標準化ワークショップ第6回学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] HLA-B27による細胞内ミスフォールド蛋白質輸送能2018

    • Author(s)
      依藤 秀樹, 荒瀬 規子, 平野 亨, 香山 雅子, 末永 忠広, 熊ノ郷 淳, 荒瀬 尚
    • Organizer
      第5回 JCRベーシックリサーチカンファレンス
    • Related Report
      2018 Annual Research Report
  • [Presentation] Recognition of DNA / HLA-class II complex by anti-DNA antibodies from SLE patients2018

    • Author(s)
      Hideaki Tsuji, Koichiro Ohmura, Shuhei Sakakibara, Noriko Arase, Masako Kohyama, Tadahiro Suenaga, Hitodhi Kikutani, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TSHR-stimulating autoantibody production by TSHR / MHC class II complexes2018

    • Author(s)
      Hui Jin, Noriko Arase, Masako Kohyama, TadahiroSuenaga, TakehikoSasazuki, HisashiArase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of T cell response by TCR-like antibodies2018

    • Author(s)
      Kazuki Kishida, Masako Kohyama,Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Deletion of iinvariant chain in adult mice resulted in autoantibody production2018

    • Author(s)
      Tatsuya Shishido, Masako Kohyama,Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of diabetogenic T cell response by antibodies against peptide-MHC class II complex2018

    • Author(s)
      Yushi Matsumoto, Kazuki Kishida, Sumiko Matsuoka, Masako Koyama, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RIFINs of Plasmodium falciparum target multiple inhibitory receptors for immune evasion2018

    • Author(s)
      Akihito Sakoguchi, Fumiji Saito, Kouyuki Hirayasu, Kyoko Shida, Masako Kohyama, TadahiroSuenaga, Shiroh Iwanaga, Toshihiro Horii, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 顕微鏡的多発血管炎におけるミエロペルオキシダーゼ/HLAクラスII分子複合体2018

    • Author(s)
      荒瀬 尚
    • Organizer
      血管炎病因病態研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ネオセルフによる新たな自己免疫疾患発症機構2018

    • Author(s)
      荒瀬 尚
    • Organizer
      埼玉関節リウマチセミナ-2018
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] HLAを標的とした免疫疾患の新たな治療法へ向けて2018

    • Author(s)
      荒瀬 尚
    • Organizer
      大阪アトピー性皮膚炎談話会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ネオセルフ化自己抗原による新たな自己免疫疾患発症機構2017

    • Author(s)
      荒瀬 尚
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cellular misfolded proteins transported to the cell surface by aberrantly expressed MHC class II molecules are major autoantibody targets in autoimmune diseases2017

    • Author(s)
      Hisashi Arase
    • Organizer
      AAI2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MHC class II-induced neo-self antigens in autoimmune diseases2017

    • Author(s)
      Hisashi Arase
    • Organizer
      RIKEN IMS-JSI International Symposium on Immunology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HLA class II-associated neo-self antigens as a target for autoimmune disease2017

    • Author(s)
      Hisashi Arase
    • Organizer
      Science Day
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 異所性MHCクラスⅡ発現によるネオセルフ抗原の生成と自己免疫疾患2017

    • Author(s)
      荒瀬 尚
    • Organizer
      第67回 日本薬学会近畿支部大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Crucial role of CD74 in hematopoietic cell differentiation2017

    • Author(s)
      Tatsuya Shishido, Masako Kohyama, Kouyuki Hirayasu, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] "Chemical compounds that specifically inhibit aberrant MHC class II expression"2017

    • Author(s)
      Yuta Shimizu, Kyoko Shida, Kouyuki Hirayasu, Masako Kohyama, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MHC: New perspectives for an old molecule2017

    • Author(s)
      Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Antigen-specific immune regulation mediated by TCR-like antibodies2017

    • Author(s)
      Kazuki Kishida, Kouyuki Hirayasu, Masako Kohyama, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Antiphospholipid antibody recognizes β2GPI complexed with HLA class II molecules via its domain V2017

    • Author(s)
      Yuki Sasagawa, Kenji Tanimura, Hui Jin, Noriko Arase, Tadahiro Suenaga, Masako Kohyama, Kouyuki Hirayasu, Satoko Morikami, Yasuhiko Ebina, Tatsuya Atsumi, Hideto Yamada, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Prothrombin complexed with HLA class II molecules is an autoantibody target in antiphospholipid syndrome2017

    • Author(s)
      Satoko Morikami, Kenji Tanimura, Noriko Arase, Kouyuki Hirayasu, Tadahiro Suenaga, Masako Kohyama, Tatsuya Atsumi, Hideto Yamada, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Recognition of SS-A/IgG/HLA-DR complex by autoantibodies in Sj_gren’s syndrome2017

    • Author(s)
      Noriko Arase, Hui Jin , Ichiro Katayama, Hisashi Arase
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Recognition of SS-A/IgG/HLA-DR complex by autoantibodies in Sj_gren’s syndrome2017

    • Author(s)
      Noriko Arase, Hui Jin, Yutaro Hayashi, Hiroyuki Murota, Hisashi Arase, Ichiro Katayama
    • Organizer
      第42回日本研究皮膚科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HLA class II-associated neo-self antigens and autoimmune diseases2017

    • Author(s)
      荒瀬 尚
    • Organizer
      第42回日本研究皮膚科学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] 免疫化学分野ホームページ

    • URL

      http://immchem.biken.osaka-u.ac.jp

    • Related Report
      2018 Annual Research Report
  • [Remarks] 大阪大学微生物病研究所免疫化学分野ホームページ

    • URL

      http://immchem.biken.osaka-u.ac.jp

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 可溶型MHCクラスⅡ分子の産生誘導組成物、可溶型MHCクラスⅡ分子の産生誘導キット、可溶型MHCクラスⅡ分子の産生細胞、可溶型MHCクラスⅡ分子の産生細胞の製造方法および可溶型MHCクラスⅡ分子の製造方法2018

    • Inventor(s)
      荒瀬 尚, 伊勢 雅子, 宍戸 達也
    • Industrial Property Rights Holder
      荒瀬 尚, 伊勢 雅子, 宍戸 達也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-228986
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2019-12-27  

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