Crystallographic analysis of the MHC class I:lipopeptide complex and identification of the lipopepitide-angigen presentation pathway

• Project/Area Number: 26860323
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Morita Daisuke 京都大学, ウイルス研究所, 助教 (40706173)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MHCクラス1 / リポペプチド / ミリスチン酸修飾 / HIV / 抗原提示 / MHCクラス１ / エイズ / ウイルス感染

Outline of Final Research Achievements

A new pathway for host defense has recently been discovered in the monkey AIDS model, in which lipopeptide-specific T cell responses develop to combat against infection. However, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. In this study, we identified a lipopepide-Ag presenting rhesus MHC class I molecule, Mamu-B*098. A high-resolution X-ray crystallographic analysis of the Mamu-B*098:lipopeptide complex reveals the detailed binding manner (Morita et al. Nature Communications 2016, doi:10.1038/ncomms10356).

Research Products

• [Journal Article] Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex. (2015)
  • Author(s): Morita D, Yamamoto Y, Mizutani T, Ishikawa T, Suzuki J, Igarashi T, Mori N, Shiina T, Inoko H, Fujita H, Iwai K, Tanaka Y, Mikami B, Sugita M,
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 10356-10356
  • DOI: 10.1038/ncomms10356
  • NAID: 120005743661
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage inducible C-type lectin, Mincle. (2014)
  • Author(s): Hattori Y, Morita, D, Fujiwara N, Mori D, Nakamura T, Harashima H, Yamasaki S, Sugita M.
  • Journal Title: The Journal of Biological Chemistry Volume: 289(22) Issue: 22 Pages: 15405-12
  • DOI: 10.1074/jbc.m114.566489
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Discovery of lipopeptide Ag-presenting molecules: its molecular identity and X-ray crystallographic structure (2015)
  • Author(s): Morita D and Sugita M.
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Discovery of a lipopeptide Ag-presenting molecule: its molecular identity and X-ray crystallographic structure (2015)
  • Author(s): Morita D and Sugita M
  • Organizer: The 10th International Symposium of the Institute Network
  • Place of Presentation: 北海道大学医学部（北海道・札幌市）
  • Year and Date: 2015-07-23
  • Int'l Joint Research
• [Remarks] N ミリストイル化リポペプチドを結合した MHCクラス1 分子複合体の結晶構造
  • URL: http://www.virus.kyoto-u.ac.jp/about/y2015/sugita201601.html
• [Remarks] 京都大学ウイルス研究所 杉田研究室ホームページ
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/SugitaLab.html