Identification of HLA class I molecules with the capacity of mediating lipopeptide presentation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21615
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kyoto University
• Principal Investigator: Sugita Masahiko 京都大学, 医生物学研究所, 教授 (80333532)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: HLA / リポペプチド

Outline of Final Research Achievements

It is generally accepted that peptides comprise a major antigen repertoire targeted by the immune system. By taking advantage of a rhesus model of human AIDS, this principal investigator previously identified immune responses directed against lipopeptides that were derived from lipid-modified viral proteins. However, it remained unknown whether such immune responses may exist in humans. In this research project, the principal investigator demonstrated that HLA-A*24:02 exhibited a previously unrecognized ability to bind lipopeptide ligands and determined a molecular priciple for lipopeptide binding by the use of X-ray crystallography. Furthermore, HLA-A*24:02-expressing transgenic mice were established, which would be valuable for in vivo analysis of HLA-A*24:02-dependent, lipopeptide-specific immune responses.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

日本人が持つHLAタイプのうち、保有率が高いHLA-A*24:02がペプチドだけでなくリポペプチドを結合することを明らかにし、その分子構造基盤を解明した。さらにHLA-A*24:02を発現した遺伝子改変マウスの樹立に成功し、今後のリポペプチド特異的T細胞応答や新たなリポペプチドワクチン開発に有用な小動物モデルを確立した。ウイルスタンパク質の脂質修飾は病原性と深く関わっており、この化学反応を検知する「リポペプチド免疫」の理解がさらに進めば、ウイルス感染制御に向けた新たな戦略が構築できる。また「リポペプチド免疫」を切り口としたヒト自己免疫病の理解と制御にも貢献する可能性がある。