Two families of Env antibodies efficiently engage Fc-gamma receptors and eliminate HIV-1-infected cells.

HIV-1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies (Abs), including anti-co-receptor binding site (CoRBS) and anti-cluster A, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further opens Env allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcγRIIIa in ELISA assays. We also show that Fc regions of both Abs are required to optimally engage Fc-RIIIa and mediate robust ADCC. Altogether, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcγRIIIa engagement and ADCC. [ABSTRACT FROM AUTHOR]