Novel strategy of host defense targeted for "viral lipopeptides"

• Project/Area Number: 18K07172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University
• Principal Investigator: Morita Daisuke 京都大学, ウイルス・再生医科学研究所, 助教 (40706173)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: MHCクラス1 / リポペプチド / ミリスチン酸修飾 / エイズ / Nef / T細胞エピトープ / リゾリン脂質 / 内在性リガンド / MHC class I / 抗原提示

Outline of Final Research Achievements

We have discovered the novel immune responses directly against lipopeptide antigens derived from N-myristoylated viral proteins, and identified a novel subset of MHC class I molecules as lipopeptide-presenting molecules (Morita et al. Nature Communications 7:10356,2016). In this study, we determined the molecular mechanism of lipopeptide-immune recognition by T cells and searched for human lipopeptide-presenting molecules for lipopeptide-vaccine development.

Academic Significance and Societal Importance of the Research Achievements

LP1分子がウイルス感染に伴い、どのようにしてウイルスリポペプチド抗原をT細胞へと提示しているのか、その分子論の詳細は不明であった。本研究によって、学術的意義として、リポペプチド免疫認識における構造学的な基盤が確立された。また、社会的意義として、リポペプチド免疫と言う新しい視点からのワクチン開発の可能性が拓かれた。同時に、ウイルス感染に伴う自己免疫疾患について、リポペプチド免疫の関連が示唆され、将来的には新しい治療法の開発へと繋がる可能性が高い。

Research Products

• [Journal Article] Crystal structure of the ternary complex of TCR, MHC class I and lipopeptides. (2020)
  • Author(s): Morita D, Iwashita C, Mizutani T, Mori N, Mikami B, Sugita M.
  • Journal Title: International Immunology Volume: 32 Issue: 12 Pages: 805-810
  • DOI: 10.1093/intimm/dxaa050
  • Peer Reviewed
• [Journal Article] Crystal structures of lysophospholipid-bound MHC class I molecules (2020)
  • Author(s): Shima Yoko、Morita Daisuke、Mizutani Tatsuaki、Mori Naoki、Mikami Bunzo、Sugita Masahiko
  • Journal Title: Journal of Biological Chemistry Volume: in press Issue: 20 Pages: 6983-6991
  • DOI: 10.1074/jbc.ra119.011932
  • Peer Reviewed
• [Journal Article] Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present N-Myristoylated 4-mer Peptides to T Cells (2019)
  • Author(s): Yamamoto Y, Morita D, Shima Y, Midorikawa A, Mizutani T, Suzuki J, Mori N, Shiina T, Inoko H, Tanaka Y, Mikami B, Sugita M.
  • Journal Title: Journal of Immunology Volume: 202 Issue: 12 Pages: 3349-3358
  • DOI: 10.4049/jimmunol.1900087
  • Peer Reviewed
• [Presentation] T-cell recognition of the lipopeptide-bound MHC class I complex; evidence from the crystal structure (2020)
  • Author(s): Morita, D., Iwashita, C., and Sugita, M.
  • Organizer: The 15th International Symposium of the Institute Network for Biomedical Sciences
  • Int'l Joint Research
• [Presentation] 霊長類研究から見えてきた、非ペプチド抗原を標的とする 新しい獲得免疫機構 (2018)
  • Author(s): 森田大輔、嶋 燿子、杉田 昌彦
  • Organizer: 第29回 日本生体防御学会学術集会
• [Presentation] リポペプチドを提示する MHC class I 分子の内因性リガンドの同定 (2018)
  • Author(s): 嶋 燿子、森田大輔、杉田 昌彦
  • Organizer: 第29回 日本生体防御学会学術集会