Regulation of cell-surface MHC-II in dendritic cells

• Project/Area Number: 25860049
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Okayama University
• Principal Investigator: FURUTA Kazuyuki 岡山大学, 医歯(薬)学総合研究科, 准教授 (50644936)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 樹状細胞 / MHC class II / Ubiquitin / Endocytosis / 小胞輸送 / MHC-II / Rab11 / Rab35 / MHCクラス II / ユビキチン / エンドサイトーシス

Outline of Final Research Achievements

Major histocompatibility complex class II (MHC-II) which expresses on dendritic cells presents antigenic peptides to CD4 T cells. The MHC-II-mediated antigen presentation initiates acquired immunity. Although the cell-surface expression of MHC-II is tightly regulated, the regulation mechanism remains to be clarified. In this study we obtained the following results: (1) Internalizing MHC-II from cell-surface is found to be targeted to the early endosome where E3 ligase MARCH-I is localized. As a result, MHC-II is ubiquitinated and targeted for lysosomal degradation. (2) Recycling of internalized MHC-II to cell-surface is found to be regulated by Rab small G protein family, Rab11 and Rab35.

Research Products

• [Journal Article] The ins and outs of MHC class II-mediated antigen processing and presentation. (2015)
  • Author(s): Roche, PA. and Furuta, K.
  • Journal Title: Nat. Rev. Immunol. Volume: 15 Issue: 4 Pages: 203-216
  • DOI: 10.1038/nri3818
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of Histamine Synthesis and Tryptase Expression through Transcription Factors, Growth Factor Independent 1 (Gfi1) and Gfi1b, in Murine Cultured Mast Cells (2014)
  • Author(s): Taura, A., Furuta, K., Yamaguchi, T., Kawabata, K., and Tanaka, S.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 37 Issue: 1 Pages: 81-86
  • DOI: 10.1248/bpb.b13-00616
  • NAID: 130003382104
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Histamine synthesis is required for granule maturation in murine mast cells. (2014)
  • Author(s): Nakazawa, S., Sakanaka, M., Furuta, K., Natsuhara, M., Takano, H., Tsuchiya, S., Okuno, Y., Ohtsu, H., Nishibori, M., Thurmond, R.L., Hirasawa, N., Nakayama, K., Ichikawa, A., Sugimoto, Y., and Tanaka, S.
  • Journal Title: Eur. J. Immunol. Volume: 44 Issue: 1 Pages: 204-214
  • DOI: 10.1002/eji.201343838
  • Peer Reviewed
• [Journal Article] Internalizing MHC class II-peptide complexes are ubiquitinated in early endosomes and targeted for lysosomal degradation. (2013)
  • Author(s): Furuta, K., Walseng, E., and Roche, P. A
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 110 Issue: 50 Pages: 20188-20193
  • DOI: 10.1073/pnas.1312994110
  • Peer Reviewed
• [Presentation] 主要組織適合抗原クラスIIのリサイクリングを制御するRabタンパク質の解析 (2015)
  • Author(s): 古田 和幸、黒田 真弘、田中 智之
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 主要組織適合抗原クラスIIのユビキチン化におけるインバリアント鎖の役割 (2014)
  • Author(s): 古田 和幸、Even Walseng、Paul Roche
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] インバリアント鎖によるMHC-IIのユビキチン化回避機構 (2014)
  • Author(s): 古田 和幸、Even Walseng、Paul Roche
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本市
• [Presentation] 活性化T 細胞による樹状細胞表面MHC-IIの発現調節機構 (2013)
  • Author(s): 古田 和幸、Paul Roche
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
• [Remarks] 岡山大学薬学部免疫生物学分野
  • URL: http://www.pharm.okayama-u.ac.jp/lab/meneki/
• [Remarks] 薬学部田中研究室 | 岡山大学
  • URL: http://www.pharm.okayama-u.ac.jp/lab/meneki/