2022 Fiscal Year Final Research Report

Mechanisms of the resistance against disease progression during bovine leukemia virus infection in cattle with DRB3*0902 allele

Research Project

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Project/Area Number	19H03128
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 42020:Veterinary medical science-related
Research Institution	University of Miyazaki
Principal Investigator	Norimine Junzo 宮崎大学, 農学部, 教授 (30627667)
Co-Investigator(Kenkyū-buntansha)	佐藤克明宮崎大学, 医学部, 教授 (40301147) 今内覚北海道大学, 獣医学研究院, 教授 (40396304)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	牛MHCクラスII / テトラマー / ヘルパーT細胞 / CD4+T細胞 / 牛白血病 / 牛伝染性リンパ腫 / プロウイルス量 / 病態進行
Outline of Final Research Achievements	Enzootic bovine leukosis is an infectious disease caused by infection of bovine leukemia virus (BLV) belonging to Retroviridae family. Purpose of this study is to understand immunological mechanisms in which DRB3 genes have been thought to play a critical role for a protective immunity and are associated with reduction of proviral load and resistance against disease progression. Among DRB3 genes, the DRB3*009:02 allele is so far most strongly associated with the protection and its tetramer was therefore generated. The epitope mapping method using this tetramer have identified several BLV-specific T cell epitopes and made possible to analyze BLV-specific helper T cells. Although experimental infection using cattle have not been achieved by the time, the tetramer generated in this study have greatly enhanced the future opportunity to clarify the mechanisms.
Free Research Field	感染症免疫学
Academic Significance and Societal Importance of the Research Achievements	牛伝染性リンパ腫ウイルス(BLV)による感染症は、ヒトT細胞白血病ウイルスI型(HTLV-1)による感染症と同様、その病態進行の機序は解明されていない。興味深い事に、BLVに感染してもDRB3009:02アリルを保有する牛は、病態が進行しない。本研究では、このアリルの４量体（テトラマー）を作製し、これを利用してBLV特異的T細胞エピトープを同定した。牛DRB3009:02のテトラマーが利用可能になった事で、このアリルが関与する抗原特異的防御免疫が解析できるようになった。特異的防御免疫の機序を明らかにすることは、類似する感染症の病態進行機序の解明そして治療法開発へつながることが期待できる。