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Analysis of function of misfolded proteins presented on MHC class II molecules.

Research Project

Project/Area Number 24659223
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

ARASE Hisashi  大阪大学, 微生物病研究所, 教授 (10261900)

Project Period (FY) 2012-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords抗原認識 / B細胞 / MHCクラスII / 自己免疫疾患 / T細胞 / 関節リウマチ / 自己抗体 / HLA-DR / MHCクラスI
Research Abstract

MHC class II molecules play an important role in immune response by presenting peptide antigens to T cells. However, we found that MHC class II molecules transport cellular misfolded proteins to the cell surface without processing to peptides. Therefore, we analyzed functions of misfolded proteins transported to the cell surface by MHC class II molecules in this study. We found that proteins presented on MHC class II molecules efficiently stimulate antigen specific B cells. Although MHC class II molecules have been thought to present peptide antigens to T cells, our findings indicate that MHC class II molecules can present protein antigens to B cells. Furthermore, when we analyzed autoantibodies from autoimmune patients, we found that proteins presented on MHC class II molecules are specifically recognized by autoantibodies. These findings suggested that misfolded proteins aberrantly presented on MHC class II molecules are a target autoimmune diseases.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (46 results)

All 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (28 results) (of which Invited: 1 results) Book (4 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Structural basis for simultaneous recognition of an O-glycan and its attached peptide of mucin family by immune receptor PILRα.2014

    • Author(s)
      Kuroki K, Wang J, Ose T, Yamaguchi M, Tabata S, Maita N, Nakamura S, Kajikawa M, Kogure A, Satoh T, Arase H, Maenaka K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111(24) Issue: 24 Pages: 8877-8882

    • DOI

      10.1073/pnas.1324105111

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of immune responses by neutrophils2014

    • Author(s)
      Wang,J.,Arase,H.
    • Journal Title

      Ann. N. Y. Acad. Sci

      Volume: (in press) Issue: 1 Pages: 66-81

    • DOI

      10.1111/nyas.12445

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages.2014

    • Author(s)
      Haldar, M., Kohyama, M., So, A.Y., Kc, W., Wu, X., Briseno, C.G., Satpathy, A.T., Kretzer, N.M., Arase, H., Rajasekaran, N.S., Wang, L., Egawa, T., Igarashi, K., Baltimore, D., Murphy, T.L., and Murphy, K.M.
    • Journal Title

      Cell

      Volume: 156 Issue: 6 Pages: 1223-1234

    • DOI

      10.1016/j.cell.2014.01.069

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility2014

    • Author(s)
      Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
    • Journal Title

      Proceedings of National Academy of Science USA

      Volume: 111 Issue: 10 Pages: 3787-3792

    • DOI

      10.1073/pnas.1401105111

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD1a-positive familial cutaneous mastocytosis without germ-line or somatic mutations in c-kit2013

    • Author(s)
      Arase, N., Wataya-Kaneda, M., Oiso, N., Arase, H., Katayama, I.
    • Journal Title

      Br. J. Dermatol.

      Volume: 169 Issue: 1 Pages: 201-204

    • DOI

      10.1111/bjd.12265

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Us3 kinase encoded by herpes simplex virus 1 mediates down regulation of cell surface major histocompatibility complex class Iand evasion of CD8+ T cells.2013

    • Author(s)
      Imai, T., et al.
    • Journal Title

      PLos One

      Volume: 8 Issue: 8 Pages: e72050-e72050

    • DOI

      10.1371/journal.pone.0072050

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules.2013

    • Author(s)
      Jiang, Y., Arase, N., Kohyama, M., Hirayasu, K., Suenaga, T., Jin, H., Matsumoto, M., Shida, K., L. Lanier, L., Saito, T. and Arase, H.
    • Journal Title

      Int. Immunol.

      Volume: 25 Issue: 4 Pages: 235-246

    • DOI

      10.1093/intimm/dxs155

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutrophil infiltration during inflammation is regulated by PILRalpha via modulation of integrin activation2012

    • Author(s)
      Wang J, et al.
    • Journal Title

      Nat Immunol

      Volume: 14 Issue: 1 Pages: 2019-2025

    • DOI

      10.1038/ni.2456

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Roles of Signal Transducer and Activator of Transcription 3 in Antitumor Immunity during Carcinogen-Induced Lung Tumorigenesis.2012

    • Author(s)
      Ihara, S., Kida, H., Arase, H., et. al.
    • Journal Title

      Cancer Res.

      Volume: 72 Issue: 12 Pages: 2990-2999

    • DOI

      10.1158/0008-5472.can-11-4062

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 病原体とペア型レセプター2013

    • Author(s)
      荒瀬尚
    • Organizer
      第67回日本細菌学会東北支部総会
    • Place of Presentation
      東北大学(宮城)
    • Year and Date
      2013-08-30
    • Related Report
      2013 Final Research Report
  • [Presentation] MHCクラスE分子と自己抗体2013

    • Author(s)
      荒瀬尚
    • Organizer
      免疫サマースクール2013
    • Place of Presentation
      ザ・ルイガンズ(福岡)
    • Year and Date
      2013-08-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Herpesvirus 6 Glycoprotein B (gB),gH,gL and gQ are Necessary and sufficient for Cell-to-Cell Fusion2013

    • Author(s)
      Tadahiro Suenaga,Yuki Tanaka,Misako Matsumoto,Tsukasa Seya,Hisashi Arase
    • Organizer
      38th International Herpesvirus Workshop
    • Place of Presentation
      Grand Rapids,Michigan (USA)
    • Year and Date
      2013-07-21
    • Related Report
      2013 Final Research Report
  • [Presentation] 水痘帯状庖疹ウイルス(VZV) glycoprotein H (gH)受容体の解析2013

    • Author(s)
      末永忠広、松本麻紀、有津史倫、森康子、荒瀬尚
    • Organizer
      第28回ヘルペスウイルス研究会
    • Place of Presentation
      淡路夢舞台国際会議場(淡路市)
    • Year and Date
      2013-05-31
    • Related Report
      2013 Final Research Report
  • [Presentation] Misfolded ER proteins transported to the cell surface by MHC class II molecules are targeted by autoantibodies2013

    • Author(s)
      Hisashi Arase
    • Organizer
      Immune Regulation by Immunoreceptors
    • Place of Presentation
      筑波大学(つくば市)
    • Year and Date
      2013-04-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Human cytomegalovirus UL10 regulates immune response via inhibitory PILRα2012

    • Author(s)
      Fuminori Arisawa,Jing Wang,Tadahiro Suenaga,Hisashi Arase
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2012-12-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Transport of misfolded ER proteins to the cell surface by MHC class II molecules2012

    • Author(s)
      Yan Jiang,Hui Jin,Masako Kohyama,Noriko Arase,Kouyuki Hirayasu,Tadahiro Suenaga,Maki Matsumoto,Kyoko Shida,Lewis L. Lanier,Takashi Saito,Ichiro Katayama and Hisashi Arase
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2012-12-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Neutrophil infiltration during inflammation is regulated by PILRa via modulation of integrin activation2012

    • Author(s)
      Jing Wang,Ikuo Shiratori,Junji Uehori,Masahito Ikawa,Hisashi Arase
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘルペスウイルス6型の膜融合はgB,gH,gL,gQによって引き起こされる2012

    • Author(s)
      田中悠喜、末永忠広、松本麻紀、森康子、荒瀬尚
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      グランキューブ大阪(大阪)
    • Year and Date
      2012-11-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 水痘帯状庖疹ウイルス(VZV)の感染におけるシアル酸の役割2012

    • Author(s)
      末永忠広、松本麻紀、有津史倫、森康子、荒瀬尚
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      グランキューブ大阪(大阪)
    • Year and Date
      2012-11-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Neutrophil infiltration during inflammation is regulated by PILRαvia modulation of integrin activation2012

    • Author(s)
      Jing Wang,Ikuo Shiratori,Junji Uehori,Masahito Ikawa & Hisashi Arase
    • Organizer
      IEIIs2012
    • Place of Presentation
      National Center of sciences Building (東京)
    • Year and Date
      2012-10-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 妊娠中の水痘初感染により子宮内胎児死亡に至った1例2012

    • Author(s)
      谷村憲司、小嶋伸恵、荒瀬尚、山田秀人
    • Organizer
      第27回ヘルペスウイルス研究会
    • Place of Presentation
      あいち健康プラザ健康宿泊館プラザホール(愛知)
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 水痘帯状庖疹ウイルス(VZV)の膜融合におけるシアル酸の役割2012

    • Author(s)
      末永忠広、松本麻紀、有津史倫、森康子、荒瀬尚
    • Organizer
      第27回ヘルペスウイルス研究会
    • Place of Presentation
      あいち健康プラザ健康宿泊館プラザホール(愛知)
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 病原体とペア型レセプター

    • Author(s)
      荒瀬尚
    • Organizer
      第67回日本細菌学会東北支部総会
    • Place of Presentation
      東北大学(仙台市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Herpesvirus 6 Glycoprotein B (gB), gH, gL and gQ are Necessary and Sufficient for Cell-to-Cell Fusion

    • Author(s)
      Tadahiro Suenaga, Yuki Tanaka, Misako Matsumoto, Tsukasa Seya, Hisashi Arase
    • Organizer
      38th International Herpesvirus Workshop
    • Place of Presentation
      Grand Rapids, Michigan (USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 水痘帯状疱疹ウイルス(VZV)glycoprotein H (gH)受容体の解析

    • Author(s)
      末永忠広、松本麻紀、有澤史倫、森康子、荒瀬尚
    • Organizer
      第28回ヘルペスウイルス研究会
    • Place of Presentation
      淡路夢舞台国際会議場(淡路市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Misfolded ER proteins transported to the cell surface by MHC class II molecules are targeted by autoantibodies

    • Author(s)
      Hisashi Arase
    • Organizer
      Immune Regulation by Immunoreceptors
    • Place of Presentation
      筑波大学(つくば市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 水痘帯状疱疹ウイルス(VZV)の膜融合におけるシアル酸の役割

    • Author(s)
      末永忠広、松本麻紀、有澤 史倫、森康子、荒瀬尚
    • Organizer
      第27回ヘルペスウイルス研究会
    • Place of Presentation
      あいち健康プラザ健康宿泊館プラザホール(愛知県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 妊娠中の水痘初感染により子宮内胎児死亡に至った1例

    • Author(s)
      谷村 憲司、小嶋 伸恵、荒瀬 尚、山田 秀人
    • Organizer
      第27回ヘルペスウイルス研究会
    • Place of Presentation
      あいち健康プラザ健康宿泊館プラザホール(愛知県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ペア型レセプターPILRのリガンド認識における糖鎖修飾の機能

    • Author(s)
      荒瀬 尚
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Glycoprotein B (gB), gH, gL, gQ1 and gQ2 of Human Herpesvirus 6 Mediate Membrane Fusion

    • Author(s)
      Yuki Tanaka, Tadahiro Suenaga, Maki Matsumoto, Yasuko Mori, Hisashi Arase
    • Organizer
      第11回あわじしま感染症・免疫フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Human cytomegalovirus UL10 regulates immune response via inhibitory PILRα

    • Author(s)
      Fuminori Arisawa, Jing Wang, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第11回あわじしま感染症・免疫フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Neutrophil infiltration during inflammation is regulated by PILRα via modulation of integrin activation

    • Author(s)
      Jing Wang, Ikuo Shiratori, Junji Uehori, Masahito Ikawa & Hisashi Arase
    • Organizer
      IEIIS2012
    • Place of Presentation
      National Center of Sciences Building, Tokyo
    • Related Report
      2012 Research-status Report
  • [Presentation] 水痘帯状疱疹ウイルス(VZV)の感染におけるシアル酸の役割

    • Author(s)
      末永 忠広、松本 麻紀、有澤 史倫、森 康子、荒瀬 尚
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      グランキューブ大阪(大阪国際会議場)(大阪府)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヘルペスウイルス6型の膜融合はgB, gH, gL, gQによって引き起こされる

    • Author(s)
      田中 悠喜、末永 忠広、松本 麻紀、森 康子、荒瀬 尚
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      グランキューブ大阪(大阪国際会議場)(大阪府)
    • Related Report
      2012 Research-status Report
  • [Presentation] Transport of misfolded ER proteins to the cell surface by MHC class II molecules

    • Author(s)
      Jiang Y, Arase N, Kohyama M, Hirayasu K, Suenaga T, Jin H, Matsumoto M, Shida K, Lanier LL, Saito T, Arase H.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Human cytomegalovirus UL10 regulates immune response via inhibitory PILRα

    • Author(s)
      Fuminori Arisawa, Jing Wang, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Neutrophil infiltration during inflammation is regulated by PILRα via modulation of integrin activation

    • Author(s)
      Jing Wang, Ikuo Shiratori, Junji Uehori, Masahito Ikawa, Hisashi Arase
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Book] 血液フロンィア2013

    • Author(s)
      荒瀬規子、荒瀬尚
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Final Research Report
  • [Book] 週刊医学のあゆみ「免疫グロブリン様受容体による免疫制御と疾患」2013

    • Author(s)
      王静、荒瀬尚
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2013 Final Research Report
  • [Book] 血液フロンティア2013

    • Author(s)
      荒瀬 規子、荒瀬 尚
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Annual Research Report
  • [Book] 週刊 医学のあゆみ「免疫グロブリン様受容体による免疫制御と疾患」2013

    • Author(s)
      王 静、荒瀬 尚
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 免疫化学分野ホームページ

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学微生物病研究所免疫化学分野

    • URL

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

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 自己抗体の検出方法、自己免疫疾患の躍患の可能性を試験する方法、自己抗体の検出試薬および自己免疫疾患用の試験試薬2013

    • Inventor(s)
      荒瀬尚、谷村憲司、金睡、荒瀬規子
    • Industrial Property Rights Holder
      荒瀬尚、谷村憲司、金睡、荒瀬規子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-148833
    • Filing Date
      2013-07-17
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 自己抗体の検出方法、自己免疫疾患の罹患の可能性を試験する方法、自己抗体の検出試薬および自己免疫疾患用の試験試薬2013

    • Inventor(s)
      荒瀬尚, 谷村憲司, 金暉, 荒瀬規子
    • Industrial Property Rights Holder
      荒瀬尚, 谷村憲司, 金暉, 荒瀬規子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-148833
    • Filing Date
      2013-07-17
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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