کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3352102 | 1216457 | 2010 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals](/preview/png/3352102.png)
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.
Journal: Human Immunology - Volume 71, Issue 2, February 2010, Pages 123–127