title: Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication.
abstract: HIV-1 mutants escaping from HLA-A- or HLA-B-restricted CTL have been well studied, but those from HLA-C-restricted CTL have not. Therefore we investigated the ability of HLA-C-restricted CTL to select HIV-1 escape mutants. In the present study, we identified two novel HLA-Cw(*) 1202-restricted Pol-specific CTL epitopes (Pol328-9 and Pol463-10). CTL specific for these epitopes were detected in 25-40% of chronically HIV-1-infected HLA-Cw(*) 1202(+) individuals and had strong abilities to kill HIV-1-infected cells and to suppress HIV-1 replication in vitro, suggesting that these CTL may have the ability to effectively control HIV-1 in some HLA-Cw(*) 1202(+) individuals. Sequence analysis of these epitopes showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was significantly associated with the HLA-Cw(*) 1202 allele and that the V9A mutant was slowly selected in the HLA-Cw(*) 1202(+) individuals. Pol 463-10-specific CTL failed both to kill the V9A virus-infected cells and to suppress replication of the V9A mutant. These results indicate that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTL. The present study strongly suggests that some HLA-C-restricted CTL have a strong ability to suppress HIV-1 replication so that they can select HIV escape mutants as in the case of HLA-A-restricted or HLA-B-restricted CTL.
authors.affiliation: Center for AIDS Research, Kumamoto University, Honjo, Kumamoto, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Honda
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.forename: Hayato
authors.initials: H
authors.lastname: Murakoshi
authors.forename: Masao
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Sakai
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Borghan
authors.forename: Takayuki
authors.initials: T
authors.lastname: Chikata
authors.forename: Madoka
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000276:immunology*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015236:HLA-C Antigens; D054302:pol Gene Products, Human Immunodeficiency Virus