Development of knowledge-based method for prediction of antigenic peptide binding to HLA

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Showa University
• Principal Investigator: Gouda Hiroaki 昭和大学, 薬学部, 教授 (60276160)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: HLA / 抗原ペプチド / 相互作用 / データベース / 免疫反応 / 重症薬疹

Outline of Final Research Achievements

Based on crystal structures of human leukocyte antigen class I (HLA-I) molecules complexed with antigenic peptides, a database (DB) of interactions between HLA-I antigen-binding pocket and antigen amino acid residue was constructed. The DB consists of (1) atomic coordinates of amino acid residues constituting the pocket, (2) coordinates of property spheres placed on the pocket, and (3) atomic coordinates of the antigen amino acid residue bound to the pocket. Five types of property spheres were used to simply describe physicochemical properties of the pocket. By retrieving pockets from the DB with similar arrangement of property spheres to that of the HLA-I pocket of interest, it is possible to predict the tendency of antigen amino acid residue to bind to the HLA-I pocket of interest. Even if a drug is bound to the HLA-I, the prediction of tendency of antigen amino acid residue to bind to the HLA-I/drug complex structure is also possible by describing the drug using property spheres.

Free Research Field

計算化学

Academic Significance and Societal Importance of the Research Achievements

ヒトの主要組織適合性複合体であるHLAクラスI(HLA-I)分子は、「自己」と「非自己」の識別などの免疫反応において重要な役割を果たしているタンパク質であり、抗原ペプチドを免疫細胞に提示する役割を担っている。また、HLA-Iに薬物が結合することで、HLA-Iが提示する抗原ペプチドが変化し、このことが重症薬疹の引き金となる可能性が示唆されている。したがって、本研究の抗原ペプチド予測手法は、自己免疫疾患などの病因解析や治療に役立つ可能性がある。