title: Coexisting members of HIV-1 p17 gene quasispecies represent proteins with distinct antigenicity and immunogenicity.
abstract: BACKGROUND
  Despite the comparatively conserved nature of the HIV-1 gag gene, countless quasispecies of the p17 gene coexist in HIV-1-infected patients. It is not known if the minor genetic differences in quasispecies will affect immune recognition.
  
  
  OBJECTIVE
  To characterize the antigenicity and immunogenicity of three different members of HIV-1 p17 quasispecies.
  
  
  METHODS
  Three members of HIV-1 p17 gene quasispecies, one from patient A (clone 9; qsA9) and two from patient E (clones 5 and 8; qsE5 and qsE8), were expressed and purified from Escherichia coli. The antigenicity of the p17 proteins was analysed using sera from HIV-1-infected individuals, and the immunogenicity was evaluated using sera and lymphocytes from primed mice of three different haplotypes.
  
  
  RESULTS
  The antigenicity of the qsE5 and qsE8 p17 recombinant proteins were distinct when tested for reactivity with human p17 antibodies. The qsE5 and qsE8 p17 were equally immunogenic in H-2d mice, but not in H-2b and H-2k mice. In H-2b mice the qsE8 protein induced higher levels of anti-p17 IgG2a, IgG2b and IgG3 than the qsE5 protein. Corroborating the IgG subclass pattern, H-2b-restricted qsE5-specific T cells produced higher in vitro levels of interferon-gamma, but not of interleukin (IL)-4, IL-5 and IL-6, than qsE8-specific T cells, suggesting a more pronounced T-helper (TH)1-like response.
  
  
  CONCLUSIONS
  The p17 gene quasispecies coexisting in the same patient at the same time may represent antigenically and immunogenically distinct proteins despite sequence homologies of above 90%. Subsequently, subtle differences between two p17 protein quasispecies are enough to prime different TH1/TH2 subsets. These findings will have implications for therapeutic HIV-1 immunizations.
authors.affiliation: Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Birk
authors.forename: J I
authors.initials: JI
authors.lastname: Flock
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: M
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015683:Gene Products, gag / Q000235:genetics* / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D017931:DNA Primers; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D011994:Recombinant Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1