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研究発表を行った学会；
・AIDS Vaccine 2010　
　２０１０年９月２８日〜１０月１日（Atlanta, USA）

タイトル；Selection of HIV-1　escape mutant by HLA-C-restricted cytotoxic T lymphocytes having a strong ability to suppress HIV-1 replication.
　
発表者；　本田　一貴　氏
　　　（熊本大学　エイズ学研究センター　滝口プロジェクト研究室）

Abstract；
Cytotoxic T lymphocytes (CTLs) play an important role in control of HIV-1 replication but cannot completely eradicate HIV-1 from HIV-1-infected individuals. It is believed that they select HIV-1 escape mutants. The escape mutants from HLA-A- or HLA-B-restricted CTLs have been well studied but those from HLA-C-restricted CTLs have not. We here investigated the ability of HLA-Cw*1202-restricted CTLs to select escape mutants. We identified two novel HLA-Cw*1202-restricted Pol-specific CTL epitopes (Pol327-9 and Pol463-10) using overlapped peptides. CTLs specific to these epitopes have a strong ability to suppress HIV-1 replication in vitro. Analysis using Elispot assay showed that T cells specific for Pol327-9 and Pol463-10 were detected in 40% of the HLA-Cw1202-positive individuals, indicating that these specific T cells are frequently elicited in chronically HIV-1-infected individuals carrying HLA-Cw*1202. Sequence analysis of these epitopes in population showed that a V-to-A substitution at the 9th position (V9A) of Pol463-10 was significantly associated with the HLA-Cw*1202 allele. In addition, a longitudinal sequence analysis of 4 HIV-1-infected HLA-Cw*1202+ individuals showed that the V9A mutant was selected over an average of 4-year period. In vitro analysis demonstrated that, Pol463-10-specific CTL clones failed to suppress replication of V9A virus although they successfully suppressed WT virus replication. These results suggest that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTLs. Furthermore we examined whether these mutations have an effect on viral fitness. The analyses using the replication kinetics and competitive assays showed that V9A virus had lower fitness than the WT virus. Indeed, 3 of 7 HLA-Cw*1202- individuals showed the reversion within approximately 2 years later. These results support the finding that the 9A mutant is not remarkably accumulating in the HLA-Cw*1202- individuals. The present study demonstrated that HLA-Cw-restricted CTLs having a strong ability to suppress HIV-1 replication selected the escape mutants.