Molecular basis for lipid presenting molecule CD1d
| Project/Area Number |
19K16051
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43020:Structural biochemistry-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Kita Shunsuke 北海道大学, 薬学研究院, 特任助教 (10702003)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | CD1 / 脂質 / αGalCer / NKT細胞 / TCR / X線結晶構造解析 / 糖脂質 / 抗原提示 / MHCクラスI / 表面プラズモン共鳴 / Saposin / 示差走査熱量測定 |
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| Outline of Research at the Start |
本研究では，CD1dによる抗原提示とNatural killer T（NKT）細胞の活性化というイベントを中心として， そこから時間的，空間的に隣接して起こるCD1dへの脂質積載や免疫制御分子（LILRB2）との関係性も含めて，立体構造解析と物理化学解析に立脚するCD1dの分子基盤を構築することを目指している．
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| 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.
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| 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。
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Report
(3 results)
Research Products
(5 results)
