Functional Activity of an HIV-1 Neutralizing IgG Human Monoclonal Antibody: ADCC and Complement-Mediated Lysis

Abstract

The IgG₁K, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF₂-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF₂ strain. Normal human serum reduced spontaneous lysis of SF₂ by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 ± 8 vs. 42 ± 8%), this still was significantly greater than lysis in media (30 ± 5%) or normal human serum (23 ± 6%) (p <.05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 ± 5 vs. 18 ± 3%) while normal mouse serum had no effect (31 ± 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 ± 8 vs. 22 ± 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 ± 9 vs. 46 ± 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16⁺ PBM population.