IgG1 b12 does not measurably direct complement activity against Env-expressing cells, while the CDC activity of enhanced Fc variants depends on the target cell. Antibodies were assayed for their abilities to bind to the surface of HIV-1JR-FL gp140 transiently expressed on HEK293F cells (A), recruit C1q to HEKJR-FL cells (B), and affect terminal complement activities targeting the antibody-opsonized HEKJR-FL cell surface, including C3 deposition (C), C5b-9 complex formation (D), and MAC-mediated lysis of two distinct Env-expressing cell models (E). Dotted lines represent average baseline complement deposition on cells in wells lacking antibody (A to D). Points and error bars represent means from technical triplicates (A to D and E, top) or from three serum donors (E, bottom) and standard deviations, respectively. Data are representative of results from at least two independent experiments.