MHC class II提示内在性抗原のFKBP51依存性新規抗原提示機構の解析

• Project/Area Number: 19590399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Azabu University (2008); Sapporo Medical University (2007)
• Principal Investigator: SAHARA Hiroeki Azabu University, 獣医学部, 教授 (10260762)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症 / FKBP51 / MHC class II / antigen presentation / antigen processing / FK506 / Hsp90

Research Abstract

我々は内在性MHC class II拘束性マイナー抗原の提示にFK506 binding protein(FKBP)51が関与していることを見出した。本研究ではFKBP51の抗原提示における分子相互機構を知るために、FKBP51 欠損COS 細胞株を作成した。その結果、抗原提示能が失われた欠損株では抗原分子の細胞内蓄積が観察されなかった。しかしながら、抗原分子内のあるモチーフ構造に変異をいれると、抗原提示量が減少し、抗原分子の細胞内の貯留がみられた(J.Immunology投稿中)。これは、野生株とFKBP51欠損株においても変化がないことから、FKBP51分子の抗原提示機構における役割はプロセッシングから提示までの過程に限定される可能性が推測された。

Research Products

• [Journal Article] Immunosuppressive effect on T cell activation by interleukin-16-and interleukin-10-cDNA-double-transfected human squamous cell line (2009)
  • Author(s): Matsumoto Y, Fujita T, Hirai I, Sahara H, Torigoe T, Ezoe K, Saito T, Cruikshank WW, Yotsuyanagi T, Sato N.
  • Journal Title: Burns 35 Pages: 383-389
  • Peer Reviewed
• [Journal Article] Molecular pathologic approaches to human tumor immunology (2009)
  • Author(s): Sato N, Hirohashi Y, Tsukahara T, Kikuchi T, Sahara H, Ichimiya S, Tamura Y and Torigoe T.
  • Journal Title: Pathol. Int. 59 Pages: 205-217
  • NAID: 10027379604
  • Peer Reviewed
• [Journal Article] Immunosuppressive effect on T cell activation by interleukin -16- and interleukin -10-cDNA-double-transfected human squamous cell line. (2009)
  • Author(s): Matsumoto, Y., et al.
  • Journal Title: Burns 35 Pages: 383-389
  • Peer Reviewed
• [Journal Article] Downregulation of Tie2 gene by a novel antitumor sulfolipid, 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG), targeting angiogenesis (2008)
  • Author(s): Mori, Y., Sahara, H., Matsumoto, K., Takahashi, N., Yamazaki, T., Ohta, K., Aoki, S., Miura, M., Sugawara, F., Sakaguchi, K., and Sato, N.
  • Journal Title: Cancer Sci. 99 Pages: 1063-1070
  • Peer Reviewed
• [Journal Article] Distruption of the association of 73 kDa heat shock cognate protein with transporters associated with antigen processing (TAP) decreases TAP-dependent translocation of antigenic peptides into the endoplasmic reticulum (2008)
  • Author(s): Kamiguchi, K., Torigoe, T., Fujiwara, O., Ohshima, S., Hirohashi, Y., Sahara, H., Hirai, I., Kohgo, Y., Sato, N.
  • Journal Title: Microbiol Immunol. 52 Pages: 94-106
  • Peer Reviewed
• [Journal Article] Downregulatlon of Tie2 gene by a novel antitumor sulfolipid, 3'-sulf oquinovosyl-1'-monoacylglycerol (SQMG), targeting angiogenesis. (2008)
  • Author(s): Mori, Y., et al.
  • Journal Title: Cancer Sci. 99 Pages: 1063-1070
  • Peer Reviewed
• [Journal Article] Disruption of the associati on of 73 kDa heat shock cognate protein with transporters associated with antigen processing (TAP) decreases TAP-dependent translocation of antigenic peptides into the endoplasmic reticulum. (2008)
  • Author(s): Kamiguchi, K., et al.
  • Journal Title: Microbiol Immunol. 52 Pages: 741-748
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP51 (2007)
  • Author(s): Imai. A., Sahara, H., Tamura, Y., Jimbow, K., Saito, T., Ezoe, K., Yotsuyanagi, T., and Sato, N.
  • Journal Title: Eur. J.Immunol. 37 Pages: 1730-1738
  • Peer Reviewed
• [Journal Article] Biological heterogeneity of the peptide binding motif of the 70-kDa heat shock protein by surface plasmon resonance analysis (2007)
  • Author(s): Maeda, H., Sahara, H., Mori, Y., Torigoe, T., Kamiguchi, K., Tamura, Y., Tamura, Y., Hirata, K., and Sato, N.
  • Journal Title: J.Biol. Chem. 282 Pages: 26956-26962
  • Peer Reviewed
• [Journal Article] Efficient cross-presentation by heat shock protein 90 peptide complex-loaded dendritic cells via an endosomal pathway (2007)
  • Author(s): Kurotaki, T., Tamura, Y., Ueda, G., Oura, J., Kutomi, G., Hirohashi, Y., Sahara, H., Torigoe, T., Hiratsuka, H., Sunakawa, H., Hirata, K., and Sato, N.
  • Journal Title: J.Immunol. 179(3) Pages: 1803-1813
  • Peer Reviewed
• [Journal Article] Effects of a new immunosuppressive agent, b-SQAG9, in swine kidney transplantation (2007)
  • Author(s): Tanaka, T., Kitamura, H., Sahara, H., Imai, A., Itoh, Y., Honma, I., Ohta, K., Sugawara, F., Sakaguchi, K., Ando, A., Inoko, H., Sato, N., and Tsukamoto, T.
  • Journal Title: Transplant Immunol. 18 Pages: 67-71
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP51. (2007)
  • Author(s): Imai. A., et. al.
  • Journal Title: Eur. J. Immunol. 37 Pages: 1730-1738
• [Journal Article] Biological heterogeneity of the peptide binding motif of the 70-kDa heat shock protein by surtace plasmon resonance analysis. (2007)
  • Author(s): Maeda, H., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 26956-26962
• [Presentation] Presentation pathway of endogenous MHC class II-restricted antigen via immunophilin FKBP51 (2008)
  • Author(s): Kamobayashi, K., Makishima, N., Suzuki, T., Suzuki, Y., Sahara,H.
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Presentation pathway of endogenous MHC class II -restricted antigen via immunophilin FKBP51. (2008)
  • Author(s): Kamobayashi. K, et al.
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2008-12-02
• [Presentation] Identification of new binding motif of HSP70 in the interaction with HLA-B*27-7-derived peptide by surface Plasmon resonance (SPR) analysis (2007)
  • Author(s): Sahara, H., et.al.
  • Organizer: 日本免疫学会
  • Place of Presentation: 東京・品川
  • Year and Date: 2007-11-20
• [Presentation] Identification of cyclosporin A binding protein CSBP that plays a critical role in hepatitis C virus genome replication (2007)
  • Author(s): Sahara, H., et.al.
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Patent(Industrial Property Rights)] シクロスポリンA結合タンパク質 (2008)
  • Inventor(s): 佐原弘益、森陽子、高橋延昭、佐藤昇志、菅原二三男、坂口謙吾、諸橋賢吾、岩端一樹、渡士幸一、下遠野邦忠、菊地浩吉、傳亘、宮下広樹
  • Industrial Property Rights Holder: 佐原弘益、森陽子、高橋延昭、佐藤昇志、菅原二三男、坂口謙吾、諸橋賢吾、岩端一樹、渡士幸一、下遠野邦忠、菊地浩吉、傳亘、宮下広樹
  • Filing Date: 2008-08-21
  • Overseas
• [Patent(Industrial Property Rights)] シクロスポリンA結合タンパク質 (2007)
  • Inventor(s): 佐原弘益、森陽子、高橋延昭、佐藤昇志、菅原二三男、坂口謙吾、諸橋賢吾、岩端一樹、渡士幸一、下遠野邦忠、菊地浩吉、傳亘、宮下広樹
  • Industrial Property Rights Holder: 佐原弘益、森陽子、高橋延昭、佐藤昇志、菅原二三男、坂口謙吾、諸橋賢吾、岩端一樹、渡士幸一、下遠野邦忠、菊地浩吉、傳亘、宮下広樹
  • Industrial Property Number: 2007-217755
  • Filing Date: 2007-08-24