| Project/Area Number |
18K06165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | T細胞 / 腫瘍免疫 / 分子イメージング / T細胞シグナル / 抗原認識 / シグナル伝達 / 細胞膜ダイナミクス |
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| Outline of Final Research Achievements |
Antigen recognition of T cell is essential for activation of acquired immunity. However, the functional analysis of individual T cells has been rarely carried out. Although many of T cell signaling related molecules has been identified, it still unknown what and how these molecules are spatio-temporally regulated upon antigen recognition. In this study, we focused on the localization and the dynamics of signaling molecules by using the combination system of antigen presenting supported membrane and high spatio-temporal resolution molecular imaging. As a result, we found the different molecular mechanism for T cell activation among the T cell subsets. These findings can be applicable for the chimeric antigen receptor (CAR)-T cell immune therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
T細胞の活性化の度合いはT細胞の抗原受容体と標的細胞の抗原との結合力によって決まると考えられている。この結合力は抗原受容体と抗原の親和性だけで議論されてきたが、本研究では共受容体も含めた複合体として考える必要性があることを明らかにした。さらに、CD8陽性キラーT細胞ではT細胞内シグナルのトリガーとなるLckを抗原受容体に集積させるために共受容体は必須であるが、CD4陽性T細胞では複合体の結合力依存的に必要性が変化することを見出した。新しいがん治療法のCAR-T細胞療法においても今回発見した原理に基づいて活性化していることが分かり、今後の治療開発への道筋が示されたと考えている。
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