Analysis of a role of Hsp90α in antigen cross presentation

• Project/Area Number: 22501027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Okayama University (2011-2012); The Institute of Physical and Chemical Research (2010)
• Principal Investigator: UDONO Heiichiro 岡山大学, 大学院・医歯薬学総合研究科, 教授 (50260659)
• Co-Investigator(Kenkyū-buntansha): 今井 孝 群馬大学, 医学部, 助教 (10513434)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Hsp90 / クロスプレゼンテーション / 樹状細胞 / ノックアウトマウス / 抗原提示 / エンドソーム / エンドゾーム / HSF-1 / Hsp90α / クロスプライミング

Research Abstract

Analysis of a role of Hsp90α in antigen cross presentation In antigen cross-presentation, dendritic cells (DCs) take up extracellular antigens (Ag) and translocate them from the endosome to the cytosol for proteasomal degradation. The molecules responsible for Ag translocation are unknown. By using Hsp90α KO mice, we demonstrated that HSP90 is essential in pulling endosomal Ag out into the cytosol.

Research Products

• [Journal Article] Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide. (2013)
  • Author(s): Eikawa, S., Kakimi, K., Idobe, M., Kuzushima, K., Luescher, I., Ohue, Y., Ikeuchi, K., Uenaka, A., Nishikawa, H., Udono, H., Oka, M., and Nakayama, E.
  • Journal Title: Int. J. Cancer Volume: 132(2) Issue: 2 Pages: 345-54
  • DOI: 10.1002/ijc.27682
  • Peer Reviewed
• [Journal Article] Phenotypic analysis of monocyte-derived dendritic cells loaded with tumor antigen with heat shock cognate protein 70. (2012)
  • Author(s): Ito S, Nagata Y, Susumu S, Yoneda A, Matsuo M, Yui K, Udono H, Eguchi S, Kanematsu.
  • Journal Title: T. Anticancer Res. Volume: 32(11) Pages: 4897-904
  • URL: http://ar.iiarjournals.org/
  • Peer Reviewed
• [Journal Article] HSP70 and HSP90 differentially regulate translocation of extracellular antigen to the cytosol for cross-presentation. (2012)
  • Author(s): Kato Y, KajiwaraC, IshigeI, MizukamiS, YamazakiC, EikawaS, KakimiK. and Udono H.
  • Journal Title: Autoimmune diseases Volume: Volume 2012 Pages: 10-10
  • DOI: 10.1155/2012/745962
  • Peer Reviewed
• [Journal Article] Spermatogenesis arrest caused by conditional deletion of Hsp90a in adult mice. (2012)
  • Author(s): Kajiwara C, Kondo S, Uda S, Dai L, Ichiyanagi T, Chiba T, Ishido S, Koji T and Udono H.
  • Journal Title: Biology Open (BIO) Volume: 1 Issue: 10 Pages: 977-982
  • DOI: 10.1242/bio.2012646
  • Peer Reviewed
• [Journal Article] HSP90α deficiency does not affect Ig gene hypermutation and class switch but causes enhanced MHC class II antigen presentation (2012)
  • Author(s): Li, Y., Li, S., Hoshino, M., Ishikawa, R., Kajiwara, C., Gao, X., Zhao, Y., Ishido, S., Udono, H., Wang, J. -Y.
  • Journal Title: Int. Immunol. Volume: 24 Issue: 12 Pages: 751-758
  • DOI: 10.1093/intimm/dxs076
  • Peer Reviewed
• [Journal Article] Differential MyD88/IRAK4 requirements for cross-priming and tumor rejection induced by hsp70-model Ag fusion protein. (2012)
  • Author(s): MizukamiS, KajiwaraC, TanakaM, KaishoT, Udono H.
  • Journal Title: Cancer Science Volume: 103 Issue: 5 Pages: 851-859
  • DOI: 10.1111/j.1349-7006.2012.02233.x
  • Peer Reviewed
• [Journal Article] Heat shock protein magic in antigen trafficking within dendritic cells - implications in antigen cross-presentation in Immunity. (2012)
  • Author(s): Udono H.
  • Journal Title: Acta Medica Okayama Volume: 66(1) Pages: 1-6
  • URL: http://ousar.lib.okayama-u.ac.jp/amo/vol66/iss1/1
  • Peer Reviewed
• [Journal Article] Heat shock protein magic in antigen trafficking within dendritic cells – implications in antigen cross-presentation in Immunity (2012)
  • Author(s): Udono H
  • Journal Title: Acta Medica Okayama Volume: 66 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Phenotypic analysis of monocyte-derived dendritic cells loaded with tumor antigen with heat shock cognate protein 70. (2012)
  • Author(s): Ito S
  • Journal Title: Anticancer Res. Volume: 32 Pages: 4897-4904
  • Peer Reviewed
• [Journal Article] Heat shock porotein magic in antigen trafficking within dendritic cells-implication in an tigen cross-presetation in Immunity (2012)
  • Author(s): Udono H
  • Journal Title: Acta Medica Okayama Volume: 66 Pages: 1-6
  • Peer Reviewed
• [Journal Article] HSP90 contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. (2011)
  • Author(s): Imai T, Kato Y, Kajiwara C, Mizukami S, Ishige I, Ichiyanagi T, Hikida M, Wang JY, Udono H.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 39 Pages: 16363-16368
  • DOI: 10.1073/pnas.1108372108
  • Peer Reviewed
• [Journal Article] Essential role of endogenous HSP90 of dendritic cells in antigen cross-presentation. (2010)
  • Author(s): Ichiyanagi T, Imai T, Kajiwara C, Mizukami S, Nakai A, Nakayama T, Udono H.
  • Journal Title: J. Immunology Volume: 185 Issue: 5 Pages: 2693-2700
  • DOI: 10.4049/jimmunol.1000821
  • Peer Reviewed
• [Journal Article] Essential role of endogenous HSP90 of dendritic cells in antigen cross-presentation. (2010)
  • Author(s): Ichiyanagi T, et al.
  • Journal Title: Journal of Immunology Volume: 185 Pages: 2693-2700
  • Peer Reviewed
• [Journal Article] Targeted inhibition of the p38 MAP kinase of IL-10-secreting CD25- T regulatory cells in cancer immunotherapy. (2010)
  • Author(s): Ohkusu-Tsukada K., et al.
  • Journal Title: Eur.J.Immunology. Volume: 40 Pages: 1011-1021
  • Peer Reviewed
• [Presentation] HSP70 and HSP90 differentially regulate translocation of extracellular antigen to the cytosol for cross-presentation. (2012)
  • Author(s): Heiichiro UDONO
  • Organizer: HSP70 and HSP90 differentially regulate translocation of extracellular antigen to the cytosol for cross-presentation.
  • Place of Presentation: Les Diablerets, Swizerland.
  • Year and Date: 2012-09-22
• [Presentation] Inhibition of regulatory T-cell migration by ELR motif-binding peptide. (2012)
  • Author(s): Shingo Eikawa, Koji Kurose, Hirofumi Matsumoto, Midori Isobe, Akiko Uenaka, Shusaku Mizukami, Chihiro Yamazaki, Yoshihiro Oheu, Mikio Oka, Heiichiro Udono, Eiichi Nakayama
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] Hsp90 existing on DC cell surface forms a chaperone complex and is involved in internalization of an antibody to Hsp90. (2012)
  • Author(s): Chihiro Yamazaki, Shusaku Mizukami, Heiichiro Udono
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] Newly vaccine strategy with mAbs against heat shock protein 90 (HSP90) on surface of antigen presenting cells. (2012)
  • Author(s): Shusaku Mizukami, Chihiro Yamazaki, Heiichiro Udono
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] 抗原提示細胞膜表面HSP90 を標的としたmAbワクチン開発の基盤的研究 (2012)
  • Author(s): 水上修作、山崎千尋、鵜殿平一郎
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-07-28
• [Presentation] Inhibition of regulatory T-cell migration by ELR motif-binding peptide. (2012)
  • Author(s): Shingo Eikawa, Koji Kurose, Hirofumi Matsumoto, Midori Isobe, Akiko Uenaka, Shusaku Mizukami, Chihiro Yamazaki, Mikio Oka, Heiichiro Udono, Eiichi Nakayama
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-07-27
• [Presentation] FcR・依存性に発現する樹状細胞膜表面シャペロン複合体 (2012)
  • Author(s): 鵜殿平一郎、水上修作、山崎千尋、榮川伸吾
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-07-27
• [Presentation] Hsp90 existing on DC cell surface forms a chaperone complex and is involved in internalization of an antibody to Hsp90. (2012)
  • Author(s): Chihiro Yamazaki, Shusaku Mizukami, Heiichiro Udono
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-07-26
• [Presentation] 抗原提示細胞膜表面HSP90 を標的としたmAbワクチンの可能性検討 (2012)
  • Author(s): 水上修作、松浦貴志、梶原千晶、宇田静葉、鵜殿平一郎
  • Organizer: 第31回岡山免疫懇話会
  • Place of Presentation: 岡山
  • Year and Date: 2012-03-07
• [Presentation] HSP70 and HSP90 differentially regulate translocation of extracellular antigen to the cytosol for cross-presentation (2012)
  • Author(s): Udono H
  • Organizer: The 6th Conference on The Hsp90 Chaperone Machine
  • Place of Presentation: Les Diablerets, Switzerland
  • Invited
• [Presentation] Dendritic cell requires HSP90 as a cytosolic translocator of extracellular antigen for cross-presentation. (2011)
  • Author(s): Heiichiro UDONO
  • Organizer: University of Michigan-RCAI Joint Workshop
  • Place of Presentation: (独)理科学研究所RCAI(横浜).
  • Year and Date: 2011-12-11
• [Presentation] Dendritic cell requires HSP90 as a cytosolic translocator of extracellularantigen for cross-presentation (2011)
  • Author(s): Udono H, et al
  • Organizer: University of Michigan-RCAI Joint Workshop
  • Place of Presentation: (独)理科学研究所RCAI(横浜)(招待)
  • Year and Date: 2011-12-11
• [Presentation] 胸腺上皮細胞株におけるbeta5 サブユニットの発現プロファイル (2011)
  • Author(s): 笠井道之、鵜殿平一郎、高浜洋介
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-29
• [Presentation] Dendritic cells require HSP90 as a cytosolic translocator of extracellular antigen for cross-presentation. (2011)
  • Author(s): Yu Kato, Takashi Imai, Chiaki Kajiwara, Shusaku Mizukami, Ikuo Ishige, Tomoko Ichiyanagi, Masaki Hikida, Wang Ji-Yang, Heiichiro Udono
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] クロスプレゼンテーションには細胞質トランスロケーターとしてのHSP90 が関与している (2011)
  • Author(s): 加藤 悠、今井 孝、梶原千晶、水上修作、石下郁夫、一柳朋子、引田正喜、王継揚、鵜殿平一郎
  • Organizer: 第6回臨床ストレス応答学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-11-05
• [Presentation] 抗原提示細胞膜表面HSP90 を標的としたmAbワクチンの可能性検討 (2011)
  • Author(s): 水上修作、松浦貴志、宇田静葉、梶原千晶、鵜殿平一郎
  • Organizer: 第6回臨床ストレス応答学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-11-05
• [Presentation] mAbs against Heat Shock Protein 90 (HSP90) on surface of antigen presenting cells. (2011)
  • Author(s): 水上修作、松浦貴志、梶原千晶、宇田静葉、鵜殿平一郎
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Dendritic cells require HSP90 as a cytosolic translocator of extracellular antigen for cross-presentation (2011)
  • Author(s): 加藤 悠、今井 孝、梶原千晶、水上修作、石下郁夫、一柳朋子、疋田正喜、王継揚、鵜殿平一郎
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] クロスプレゼンテーションには細胞質トランスロケーターとしてのHSP90 が必須である (2011)
  • Author(s): 加藤 悠、今井 孝、梶原千晶、水上修作、石下郁夫、一柳朋子、引田正喜、王継揚、鵜殿平一郎
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-06-30
• [Presentation] mAbを用いた抗原提示細胞膜表面HSP90 の解析とワクチンの可能性検討 (2011)
  • Author(s): 水上修作、松浦貴志、梶原千晶、宇田静葉、鵜殿平一郎
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-06-30
• [Presentation] 抗原提示細胞膜表面HSP90を標的としたmAbワクチンの可能性検討 (2010)
  • Author(s): 水上修作, et al.
  • Organizer: 第5回 臨床ストレス応答学会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-20
• [Presentation] mAb-mediated targeting of surface HSP90 on APCs enables efficient cross-presentation and induces cytotoxic T cell immunity. (2010)
  • Author(s): 水上修作, et al.
  • Organizer: 第61回 日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] ヒト26Sプロテアソームのリン酸化による機能調節 (2010)
  • Author(s): 木村弥生, et al.
  • Organizer: 第61回 日本電気泳動学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-18
• [Presentation] HSC70-NY-ESO-1 fusion protein could induce CTL in A2 transgenic mouse (2010)
  • Author(s): 水上修作, et al.
  • Organizer: 第14回 国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] Arole of endogenous Hsp90 of dendritic cells in antigen cross-presentation (2010)
  • Author(s): 今井孝, et al.
  • Organizer: 第14回 国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] 抗原提示細胞膜表面Hsp90に対するmAbワクチンの可能性検討 (2010)
  • Author(s): 水上修作, et al.
  • Organizer: 第14回 日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-22
• [Book] 熱ショックタンパク質と交差抗原提示機構、第84 巻 第10号 (2012)
  • Author(s): 鵜殿平一郎
  • Publisher: 生化学
• [Book] 臨床免疫・アレルギー科樹状細胞による交差抗原提示とHSP. 58(2) (2012)
  • Author(s): 山崎千尋、鵜殿平一郎
• [Book] 熱ショックタンパク質と交差抗原提示機構 (2012)
  • Author(s): 鵜殿平一郎
  • Total Pages: 11
  • Publisher: 生化学
• [Book] 樹状細胞による交差抗原提示とHSP (2012)
  • Author(s): 山崎千尋
  • Total Pages: 5
  • Publisher: 臨床免疫・アレルギー科
• [Remarks] 1.化学工業日報2011年9月20日抗原提示のしくみ解明たん白質Hsp90免疫認識機構に必須
• [Remarks] 2.日経産業新聞2011年9月28日免疫系、がん細胞認識し攻撃必須たんぱく質特定
• [Remarks] 3.山陽新聞2011年9月20日免疫活性化に特定タンパク
• [Remarks] 4.読売新聞2011年12月19日免疫細胞活性化に介添えたんぱく質
• [Remarks] 5.日経プレスリース2011年9月20日タンパク質の折り畳みを助ける「Hsp90」が免疫機構でも機能を発揮-樹状細胞ががんやウイルス抗原を取り込み、抗原提示する仕組みを解明-
• [Remarks] 6.RIKEN Research Highlight 2012/02/03 "Holding back Immunity"
• [Remarks] ホームページ
  • URL: http://www.okayama-u.ac.jp/user/immuno/research.html
• [Remarks]
  • URL: http://www.riken.go.jp/r-world/info/release/press/2011/110920/index.html
• [Remarks]
  • URL: http://www.riken.go.jp/r-world/research/lab/rcai/chape/index.html
• [Patent(Industrial Property Rights)] 新規抗 HSP90 モノクローナル抗体 NOVEL ANTI-HSP90 MONOCLONAL ANTIBODY (2011)
  • Inventor(s): 鵜殿平一郎、水上修作
  • Industrial Property Rights Holder: (独)理化学研究所
  • Filing Date: 2011-04-13
  • Overseas
• [Patent(Industrial Property Rights)] 新規抗Hsp90モノクローナル抗体 (2010)
  • Inventor(s): 鵜殿平一郎、水上修作
  • Industrial Property Rights Holder: (独)理化学研究所
  • Filing Date: 2010-04-13
  • Overseas