Detection and characterization of dual-TCR T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19371
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Nitta Takeshi 東京大学, 大学院医学系研究科(医学部), 准教授 (30373343)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: T細胞 / 抗原受容体 / TCR / マウス / ゲノム編集

Outline of Final Research Achievements

A subpopulation of T cells express two T cell receptor (TCR) alpha chains, although the nature and immunological significance of such dual-TCR T cells has been poorly understood. In this study, we generated mice with reporter genes linked via 2A peptides to the constant region of the TCRa gene, to evaluate dual-TCR T cells in vivo. In addition, the mice with epitope tags inserted at the extracellular site of the constant region of TCRa were generated, to distinguish ‘holo dual-TCR T cells’, which express two TCRa on the cell surface, and ‘hemi dual-TCR T cells’, which express one TCRa and keep another TCRa inside the cell. Using these mice, we demonstrated the in vivo distribution of dual-TCR T cells in steady state as well as during immune responses.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

近年、二重特異性（bispecific）抗体やキメラ抗原受容体（CAR）を用いるがん免疫治療など、免疫系の抗原特異的作用を治療に応用する試みが注目を集めている。本研究の目標であるDual-TCR細胞の意義の解明は、T細胞の基礎的性状を理解するにとどまらず、２種類の抗原特異性を示すT細胞を医療に応用する可能性につながる。Dual-TCR T細胞は自己免疫疾患や移植片対宿主病（GVHD）に関与することが指摘されている。本研究で確立したモデル動物と、dual-TCR細胞に関する新知見は、それらの疾患に関するよりよい理解と新規の治療戦略に繋がると期待される。