title: Enhanced Recognition of HIV-1 Cryptic Epitopes Restricted by HLA Class I Alleles Associated With a Favorable Clinical Outcome.
abstract: BACKGROUND
  Cryptic epitopes (CEs) are peptides derived from the translation of 1 or more of the 5 alternative reading frames (ARFs; 2 sense and 3 antisense) of genes. Here, we compared response rates to HIV-1-specific CE predicted to be restricted by HLA-I alleles associated with protection against disease progression to those without any such association.
  
  
  METHODS
  Peptides (9mer to 11mer) were designed based on HLA-I-binding algorithms for B*27, B*57, or B*5801 (protective alleles) and HLA-B*5301 or B*5501 (nonprotective allele) in all 5 ARFs of the 9 HIV-1 encoded proteins. Peptides with >50% probability of being an epitope (n = 231) were tested for T-cell responses in an IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay. Peripheral blood mononuclear cell samples from HIV-1 seronegative donors (n = 42) and HIV-1 seropositive patients with chronic clade B infections (n = 129) were used.
  
  
  RESULTS
  Overall, 16%, 2%, and 2% of chronic HIV infected patients had CE responses by IFN-γ ELISpot in the protective, nonprotective, and seronegative groups, respectively (P = 0.009, Fischer exact test). Twenty novel CE-specific responses were mapped (median magnitude of 95 spot forming cells/10 peripheral blood mononuclear cells), and most were both antisense derived (90%) and represented ARFs of accessory proteins (55%). CE-specific CD8 T cells were multifunctional and proliferated when assessed by intracellular cytokine staining.
  
  
  CONCLUSIONS
  CE responses were preferentially restricted by the protective HLA-I alleles in HIV-1 infection, suggesting that they may contribute to viral control in this group of patients.
authors: *Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; and †Microsoft Research, Redmond, WA.
authors: Anju
authors: A
authors: Bansal
authors: Tiffanie
authors: T
authors: Mann
authors: Sarah
authors: S
authors: Sterrett
authors: Binghao J
authors: BJ
authors: Peng
authors: Anne
authors: A
authors: Bet
authors: Jonathan M
authors: JM
authors: Carlson
authors: Paul A
authors: PA
authors: Goepfert
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma