Toward a new understanding of acquired immune system via structural analysis of MHC-crossreative T cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19452
• 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: Hiroshima University
• Principal Investigator: ICHINOHE TATSUO 広島大学, 原爆放射線医科学研究所, 教授 (80314219)
• Co-Investigator(Kenkyū-buntansha): 本庶 仁子 広島大学, 原爆放射線医科学研究所, 講師 (80614106)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: T細胞受容体 / 立体構造 / 交差反応性 / 免疫シーケンシング / シングルセルゲノミクス

Outline of Final Research Achievements

In this study, we accumulated approximately 2.3 million T-cell receptor (TCR) beta chain clonotypes from peripheral blood in recipients of allogeneic hematopoietic cell transplantation (HCT). Of these clonotypes, 42,436 (1.5%) were proven to be shared between different recipients. Notably, whole T-cell repertoires of post-HCT recipients were predominated by “shared TCR clonotypes” irrespective of donor-recipient HLA compatibility. As a good example, we also identified two HLA-B7-restricted CMV-reactive TCR clonotypes in the TCR repertoire of HLA-B7-negative recipients. Additionally for in toto analysis of T-cell reconstitution at the individual level, we have created an MHC-partially mismatched zebrafish HCT model and found that predominant TCR clonotypes in post-transplant recipients were substantially different from those in donor graft.

Free Research Field

血液免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて得られた知見は、「共有TCR」がMHC交差的(crossreactive)に免疫学的優位性を保有する可能性を示唆するものであり、「単一レセプター単一抗原」に代わる獲得免疫系の新たな理解への道を開くものとして、学術的に重要な意義を有する。また、本研究で開発を行ったTCR遺伝子導入用の非ウイルスベクターはわが国独自の技術による遺伝子改変T細胞医薬品の開発に貢献し得る。