Fig. 7.

Correlations between angle of the Fc in relation to target cell surface and ADCC activities. a Models of putative immune-complexes formed by CoRBS antibodies at the target/effector cell interface were assembled as described previously [55]. Virion position modeled based on a cryo-EM structure of 17b bound to a d1-d2 CD4-triggered Env trimer. Four-domain CD4 was generated by superimposing four-domain CD4 (PDB code: 1WIO) onto d1-d2 domains of CD4 in the complex, 17b IgG was built by superimposition of monoclonal murine antibody subclass IgG1 (PDB code 1IGY) onto the 17b Fab (space fill model, green). There are two possible orientations: the main figure shows the complex formed by engagement of Fab 1 with the alternate complex formed through Fab 2 in the box above each view. Human FcγRIII receptor (residues 1–172) was added by overlaying the Fc-FcγRIII complex (PDB code 1E4K) onto Fc domain of the modeled IgG (ribbon diagram, blue for 17b). Analogous models were built for N12-i2, 412d, X5, and 48d for putative position of the human Fcγ receptor bound to Fc in the immune-complexes, for clarity only the FcγRIII receptors are shown; red: N12-i2, cyan: 412d, orange: X5 and yellow: 48d. The left panel shows the putative position of the effector cell with angle of attack by which the effector cell targets the Fc region of each mAb, shown by arrows. Range of FcγIII receptor positions depending on modeled mAb is indicated by a green double-sided arrow. Both orientations of the IgG place the FcγRIII receptor bound to N12-i2 (red) in a favorable orientation for Fc-effector cell access. b Correlations between Fc binding angle ADCC—maximum lysis (left) and AUC (right). c Correlation between Fc binding angles and ADCC of NL43/ADA/N-U- infected cells—maximum lysis (left panel) and AUC (right panel). d Correlations between Fc binding angles and % lysis of NL43/ADA/N-U- target cells at concentration of 0.1 μg/ml. *P < 0.05 via two-tailed Pearson correlation