Sex-mismatched hematopoietic cell transplantation and acquisition of B-cells specific to antigens on Y-chromosome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Nakasone Hideki 自治医科大学, 医学部, 教授 (50757903)
• Co-Investigator(Kenkyū-buntansha): 神田 善伸 自治医科大学, 医学部, 教授 (30334379)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 性別不一致移植 / HY免疫

Outline of Final Research Achievements

In this study, we have been periodically storing post-transplant patient specimens and focusing on immune responses to minor histocompatibility antigens, specifically targeting the Y chromosome antigen (HY antigen) in sex-mismatched transplants, especially combinations involving female donors and male recipients. We considered regions with amino acid sequence differences between the Y chromosome antigen and its counterpart, the X chromosome antigen, as target sites for HY immunity. We were able to synthesize fluorescent dye complexes with custom peptides, identify regions on HLA that are more likely to present, and perform tetramer synthesis. Additionally, using clinical data, we were able to demonstrate the presence of anti-HY immune effects on graft-versus-leukemia. We plan to continue actively disseminating knowledge of HY immunity while accumulating cases in the future.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

期間を通じて、マイナー抗原であるY染色体抗原に対する免疫応答（HY免疫）が性別不一致後の抗腫瘍効果の減弱・腫瘍免疫回避に関わる可能性を臨床的に初めて示し、抗HY免疫による移植片対白血病効果の存在を示すことができた。本研究で得られた知見は、同種造血細胞移植のドナー選択における戦略を考える際の大きな助けとなる。