Coexisting members of HIV-1 p17 gene quasispecies represent proteins with distinct antigenicity and immunogenicity

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-2-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-2(d) mice, but not in H-2(b) and H-2(k) mice. In H-2(b) mice the qsE8 protein induced higher levels of anti-p17 IgG2a, IgG2b and IgG3 than the qsE5 protein. Corroborating the IgG subclass pattern, H-2(b)-restricted qsE5-specific T cells produced higher in vitro levels of interferon-gamma, but not of interleukin (IL)-4, 1L-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. (C) 1998 Lippincott Williams & Wilkins.