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  • Title: Coexisting members of HIV-1 p17 gene quasispecies represent proteins with distinct antigenicity and immunogenicity.
    Author: Birk M, Flock JI, Sönnerborg A, Sällberg M.
    Journal: AIDS; 1998 Oct 22; 12(15):1973-81. PubMed ID: 9814865.
    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.
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