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

• Project/Area Number: 24659223
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka 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: ¥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.

Research Products

• [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
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of immune responses by neutrophils (2014)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] CD1a-positive familial cutaneous mastocytosis without germ-line or somatic mutations in c-kit (2013)
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Neutrophil infiltration during inflammation is regulated by PILRalpha via modulation of integrin activation (2012)
  • Author(s): Wang J, et al.
  • Journal Title: Nat Immunol Volume: 14 Issue: 1 Pages: 2019-2025
  • DOI: 10.1038/ni.2456
  • 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
  • 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
• [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
• [Presentation] Herpesvirus 6 Glycoprotein B (gB),gH,gL and gQ are Necessary and sufficient for Cell-to-Cell Fusion (2013)
  • 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
• [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
• [Presentation] Misfolded ER proteins transported to the cell surface by MHC class II molecules are targeted by autoantibodies (2013)
  • 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
• [Presentation] Human cytomegalovirus UL10 regulates immune response via inhibitory PILRα (2012)
  • 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
• [Presentation] Transport of misfolded ER proteins to the cell surface by MHC class II molecules (2012)
  • 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
• [Presentation] Neutrophil infiltration during inflammation is regulated by PILRa via modulation of integrin activation (2012)
  • 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
• [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
• [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
• [Presentation] Neutrophil infiltration during inflammation is regulated by PILRαvia modulation of integrin activation (2012)
  • 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
• [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
• [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
• [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）
  • 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)
• [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）
• [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）
• [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)
• [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)
• [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)
• [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）
• [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）
• [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
• [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)
• [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)
• [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）
• [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）
• [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）
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/index.html
• [Remarks] 免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp/
• [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/
• [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
• [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