title: Escape mutation selected by Gag28-36-specific cytotoxic T cells in HLA-A*2402-positive HIV-1-infected donors.
abstract: Gag-specific CTLs are known to have stronger ability to control HIV-1 replication than others that are protein-specific. Therefore, the analysis of Gag escape mutants is expected to clarify the mechanisms of immune control in HIV-1-infected donors. However, only a limited number of Gag escape mutants have been identified so far. A previous study suggested the possibility that Gag28-3R (KW9-3R) is an escape mutant from HLA-A*2402-restricted KW9-specific CTLs but did not show any evidence of it. Here we sought to demonstrate that KW9-3R is selected as escape mutant by KW9-specific CTLs. KW9-specific CTLs showed a remarkable reduction in recognition of target cells infected with the KW9-3R mutant. The sequence analysis of HIV-1 from 58 HIV-1-infected individuals showed that the frequency of the KW9-3R mutant was significantly higher in HLA-A*2402(+) individuals than in HLA-A*2402(-) individuals. Longitudinal analysis of an HLA-A*2402(+) individual with HIV-1 early infection showed that this escape mutant was selected over an approximately 2-year period. These results together indicate that Gag28-3R is an escape mutant selected by HLA-A*2402-restricted KW9-specific CTLs. Further analysis of this epitope will clarify the role of HIV-1-specific CTLs in the control of HIV-1 among the Japanese population, since 70% of them carry this allele.
authors.affiliation: Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Koizumi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Iwatani
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.forename: Mamoru
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Taisuke
authors.initials: T
authors.lastname: Izumi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus