Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals.
Most escape mutations have been identified on cytotoxic T lymphocyte (CTL) epitopes presented by Caucasian or African human leukocyte antigen (HLA) class I alleles, whereas a limited number of studies have identified the escape mutations on epitopes presented by Asian alleles. HLA-B54 is a common HLA allele in Asian countries. We recently identified five HLA-B*5401-restricted HIV-1-specific CTL epitopes. We here investigated escape mutations in these CTL epitopes in Japanese HIV-1-infected individuals. The frequency of substitution from Glu (E) to Asp (D) at position 7 (FV9-7D) in the Pol 154-162 (FV9) epitope was significantly higher in HLA-B*5401(+) HIV-infected individuals than in HLA-B*5401(-) individuals, whereas substitutions that were significantly higher in HLA-B*5401(+) individuals than in HLA-B*5401(-) individuals were not found in the other four epitopes. FV9-specific CTLs showed reduced killing activity against target cells pulsed with the FV9-7D mutant peptide and failed to kill those infected with the FV9-7D mutant virus, strongly suggesting that FV9-7D is an escape mutant. Furthermore, longitudinal sequence analysis of the FV9 epitope in two HLA-B*5401(+) individuals revealed that the sequence had changed from the wild type to the FV9-7D during the clinical course. Taken together, these results indicate that the FV9-7D escape mutant had been selected by FV9-specific CTLs among chronically HIV-1-infected HLA-B*5401(+) individuals.
Hashimoto
Masao
M
Division of Viral Immunology, Centers for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Kitano
Mitsutaka
M
Honda
Kazutaka
K
Koizumi
Hirokazu
H
Dohki
Sachi
S
Oka
Shinichi
S
Takiguchi
Masafumi
M
D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C113783:HLA-B54 antigen