Molecular basis for lipid presenting molecule CD1d

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16051
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Hokkaido University
• Principal Investigator: Kita Shunsuke 北海道大学, 薬学研究院, 特任助教 (10702003)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: CD1 / 脂質 / αGalCer / NKT細胞 / TCR / X線結晶構造解析

Outline of Final Research Achievements

This study focuses on the events of antigen presentation by CD1d and activation of Natural killer T (NKT) cells, and the relationship between lipid loading on CD1d and immunoregulatory molecules. The purpose of this study is to construct the molecular basis of CD1d based on three-dimensional structure analysis and biophysical analysis such as surface plasmon resonance and differential scanning calorimetry. As the result, the X-ray crystal structure of the CD1d and αGalCer derivative complex was determined. From the structure, important knowledge for antigen recognition mechanism of CD1d was obtained. Further protein-protein interactions between CD1d and immune cell receptors were analyzed. Taken together, molecular basis of CD1d including three dimentional structure and protein-protein interaction was established and that could confer important knowledge for the application of CD1d molecule as biological therapy.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ガン細胞を攻撃するNKT細胞の働きを制御する分子CD1dについて研究を行った。CD1dは脂質と結合した後、NKT細胞に認識されるとNKT細胞が活性化する。本研究ではCD1dと脂質複合体の立体構造解析やCD1dと他の分子との結合の有無などを調べ、CD1dの生体内での機能をより深く理解することに成功した。本研究の成果は、CD1dと脂質の組み合わせによって免疫を制御する可能性を秘めており、将来、患者の免疫力を利用してガンの治療を行うために応用されることを期待している。