Aspects of molecular interaction between HIV p17 and human gamma interferon

We describe the specific interaction between high-purity recombinant human immunodeficiency virus (HIV) type 1 p17 and human gamma interferon (hIFN-gamma) proteins. This interaction was found to be dose dependent and to involve conformational epitopes on both sides. Specificity was confirmed by competition ELISA, using monoclonal antibodies (MAbs) to hIFN-gamma as specific reagents. By competition experiments we also identified the epitope(s) on the hIFN-gamma molecule involved in p17 binding, very close to the receptor binding site, The kinetic constants were determined by surface plasmon resonance (SPR) analysis. The affinity constant (K-A) of the complex was 2.78 x 10(8) M(-1), that is, the ratio between a low dissociation rate constant (K-off)(1 x 10(-5)sec(-1)) and a high association rate constant (K-on) (3 x 10(3)M(-1)sec(-1)). However, p17 did not displace the binding of hIFN-gamma to its cellular receptor, nor did it interfere with the capability of the lymphokine to induce de nova expression of HLA-DR antigens on human monocytic cells or to inhibit the proliferation of tumor cells.