Identification and functional analysis of a novel class of human MHC class I molecules presenting lipopeptide antigens

• Project/Area Number: 16K19151
• 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・再生医科学研究所, 助教 (40706173)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MHCクラス1 / リポペプチド / Nef / ミリスチン酸修飾 / エイズ

Outline of Final Research Achievements

In contrast to peptide Ag-presentation mediated by conventional MHC class I, a new pathway for host defense has been discovered in the monkey AIDS model, in which N-myristoylaed viral lipopeptide-specific T cell responses develop to combat against infection. We has identified novel rhesus MHC class I (LP1) molecules as lipopeptide-presenting molecules and determined the X-lay crystal structures of rhesus LP1 complexed with lipopeptide at high resolution (Morita et al. Nature Communications 7:10356,2016). In the basis of the detailed structural information, we has completed to select human LP1 candidate molecules by in silico database searching and the mutant analysis, which was likely to be capable of binding lipopeptide Ags.

Research Products

• [Journal Article] Neutrophils and the S100A9 protein critically regulate granuloma formation (2016)
  • Author(s): Yuya Yoshioka, Tatsuaki Mizutani, Satoshi Mizuta, Ayumi Miyamoto, Satoru Murata, Toshiaki Ano, Hiroshi Ichise, Daisuke Morita, Hiroyuki Yamada, Yoshihiko Hoshino, Tatsuaki Tsuruyama and Masahiko Sugita
  • Journal Title: Blood Advances Volume: 1 Issue: 3 Pages: 184-192
  • DOI: 10.1182/bloodadvances.2016000497
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] リポペプチド：エイズウイルス制御の新しい免疫標的分子 (2018)
  • Author(s): 森田大輔
  • Organizer: 日本薬学会第138年会
• [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] Discovery of N-myristoylated lipopeptide Ag-presenting MHC class I molecules. (2016)
  • Author(s): Morita D
  • Organizer: The 23rd East Asia Joint Symposium
  • Place of Presentation: Taipei (Taiwan)
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] 「リポペプチド免疫応答」の発見とその分子機構の解明 (2016)
  • Author(s): 森田大輔、杉田昌彦
  • Organizer: 第２７回日本生体防御学会学術集会
  • Place of Presentation: 九州大学 病院キャンパス内 コラボステーションI（福岡県・福岡市）
  • Year and Date: 2016-07-07
• [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