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2021 Fiscal Year Final Research Report

Spatiotemporal mechanism in T cell signaling regulated by cell membrane dynamics

Research Project

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Project/Area Number 18K06165
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43040:Biophysics-related
Research InstitutionTokyo Medical University

Principal Investigator

Machiyama Hiroaki  東京医科大学, 医学部, 講師 (40704606)

Project Period (FY) 2018-04-01 – 2022-03-31
KeywordsT細胞 / 腫瘍免疫 / 分子イメージング
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.

Free Research Field

1細胞免疫学

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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Published: 2023-01-30  

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