title: The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection.
abstract: BACKGROUND
  The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.
  
  
  METHODS
  14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and (51)Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed.
  
  
  RESULTS
  29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard (51)Cr release assay.
  
  
  CONCLUSIONS
  CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design.
authors: Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors: Busarawan
authors: B
authors: Sriwanthana
authors: Masahiko
authors: M
authors: Mori
authors: Mari
authors: M
authors: Tanaka
authors: Sei
authors: S
authors: Nishimura
authors: Toshiyuki
authors: T
authors: Miura
authors: Panita
authors: P
authors: Pathipvanich
authors: Pathom
authors: P
authors: Sawanpanyalert
authors: Koya
authors: K
authors: Ariyoshi
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D019295:Computational Biology; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D022223:Vaccines, Subunit; D054301:gag Gene Products, Human Immunodeficiency Virus