Study on HIV-1-specific cytotoxic T lymphocytes responsible for AIDS progression in HIV-1-infected individuals

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19588
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: MURAKOSHI HAYATO 熊本大学, エイズ学研究センター, 特任講師 (60646123)
• Research Collaborator: GATANAGA Hiroyuki ; CHIKATA Takayuki ; AKAHOSHI Tomohiro
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 細胞傷害性T細胞 / HIV / HLA

Outline of Final Research Achievements

To clarify this mechanism, we identified HLA-B*35:01-restricted epitope-specific CD8+ T cells controlling HIV-1 in 63 HIV-1 clade B-infected Japanese individuals having HLA-B*35:01 and further analyzed the effect of mutations within the epitopes on the T cell responses. The T cell responses to GagNY9, PolVY10, NefRY11, or YF9 epitopes were significantly associated with low plasma viral load. A breadth of the T cell responses to these 4 epitopes was inversely correlated with it. The control of HIV-1 by YF9-specific T cells are impaired by NefY135F mutation associated with HLA-A*24:02. The ex vivo longitudinal analysis of the YF9-specific T cells showed that the Y135F mutant-specific T cells and wild type-specific/cross-reactive T cells were elicited before and after an emergence of the mutant virus. However, the former T cells failed to control HIV-1 replication whereas the latter T cells contributed to the control of HIV-1.

Free Research Field

感染免疫学