Paradigm shift in antigen recognition of T cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19441
• 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: University of Toyama
• Principal Investigator: Kishi Hiroyuki 富山大学, 学術研究部医学系, 教授 (60186210)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: T細胞受容体 / 抗原認識 / シス相互作用

Outline of Final Research Achievements

Macrophages that phagocytose pathogenic microorganisms, or virus-infected cells degrade bacterial or viral proteins into peptides and present them on the cell surface by binding them onto the major histocompatibility complex (MHC) molecules on the cells. T cells use the T cell receptors (TCR) to recognize MHC molecule/peptide complexes on the target cells and eliminate viruses and bacteria from the body. In this context, the TCR interacts with MHC molecule/peptide complexes on the surface of different cells. In this study, we showed that antigenic protein-derived peptides expressed in T cells is presented to the MHC molecules on the T cells, interacts with the same cell surface TCR (cis-interaction), and activates the T cells. Furthermore, the application of cis-interaction of TCR and MHC/peptide complexes was investigated.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

従来、T細胞は、TCRを用いて、標的細胞上のMHC分子／ペプチド複合体を認識することが知られていた(trans相互作用)。本研究により、T細胞上のTCRが自分自身のMHC分子／ペプチド複合体とcisの相互作用をすることで活性化しうることが示されたことで、今後、T細胞の活性化を考える際に、transの相互作用に加えてcisの相互作用の可能性も同時に考える必要がある。また、cisの相互作用を用いた抗原同定法や抗原特異的T細胞の同定法によりT細胞の解析がより進展すると期待される。