Lipopeptide Immunity: A novel approach to autoimmunity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07078
• 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, 医生物学研究所, 助教 (40706173)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: MHCクラス1 / HLA / リポペプチド / ミリスチン酸修飾 / エイズ / 自己免疫

Outline of Final Research Achievements

We have identified a novel subset of MHC class I molecule, LP1 that presents virus-derived lipopeptides to T cells and have elucidated their structures and functions. On the other hand, lipopeptide immunity is theoretically difficult to distinguish between self and non-self due to its ambiguous antigen specificity, suggesting its potential involvement in the exacerbation of human autoimmunity associated with viral infection. Therefore, based on the structural information from the known LP1 molecules, we identified HLA-A*2402 and HLA-C*1402, which are the most frequent alleles in the Japanese population, as LP1 candidates, and determined their X-ray crystal structures at a high resolution. Furthermore, we have established mouse lines that recapitulate lipopeptide immunity. Utilizing these unique animal models, we are investigating the relationship between viral infection and autoimmunity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

病原体抗原と自己抗原の間に構造類似性がある時、両者の間に免疫学的な交差反応が起こり、自己反応性が生じ得る。従来、この概念は蛋白やペプチド抗原に対する免疫の枠組みの中で理解されてきたが、リポペプチド抗原を特異的に認識するT細胞は、自己と非自己の識別が本質的に困難であることから、自己免疫病態の発露に関わっている可能性が高い。本研究が成就すれば、自己免疫の新概念が生み出され（学術的意義）、リポペプチドを標的とした新しい治療法・予防法・診断法の開発に繋がる（社会的意義）。