PMID- 19891998 OWN - NLM STAT- MEDLINE DCOM- 20100407 LR - 20100201 IS - 1879-1166 (Electronic) IS - 0198-8859 (Linking) VI - 71 IP - 2 DP - 2010 Feb TI - Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals. PG - 123-7 LID - 10.1016/j.humimm.2009.10.015 [doi] AB - 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. CI - Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. FAU - Hashimoto, Masao AU - Hashimoto M AD - Division of Viral Immunology, Centers for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. FAU - Kitano, Mitsutaka AU - Kitano M FAU - Honda, Kazutaka AU - Honda K FAU - Koizumi, Hirokazu AU - Koizumi H FAU - Dohki, Sachi AU - Dohki S FAU - Oka, Shinichi AU - Oka S FAU - Takiguchi, Masafumi AU - Takiguchi M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091103 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B54 antigen) SB - IM MH - Chronic Disease MH - Epitopes, T-Lymphocyte/*genetics/immunology MH - HIV Infections/*genetics/*immunology MH - HIV-1/genetics/immunology MH - HLA-B Antigens/*genetics/immunology MH - Humans MH - Mutation MH - T-Lymphocytes, Cytotoxic/*immunology/virology EDAT- 2009/11/07 06:00 MHDA- 2010/04/08 06:00 CRDT- 2009/11/07 06:00 PHST- 2009/07/03 00:00 [received] PHST- 2009/10/06 00:00 [revised] PHST- 2009/10/27 00:00 [accepted] PHST- 2009/11/07 06:00 [entrez] PHST- 2009/11/07 06:00 [pubmed] PHST- 2010/04/08 06:00 [medline] AID - S0198-8859(09)00631-4 [pii] AID - 10.1016/j.humimm.2009.10.015 [doi] PST - ppublish SO - Hum Immunol. 2010 Feb;71(2):123-7. doi: 10.1016/j.humimm.2009.10.015. Epub 2009 Nov 3.