Figure 1. Epitope mapping of CD4bs antibodies.

A panel of gp120 core point mutants was used to epitope map CD4bs antibodies (n = 25). Representative mAbs from 4 groups, including weakly neutralizing (wnAbs), vaccine-induced, and broadly neutralizing (bnAb) antibodies were evaluated. (A) The sensitivity of various mAbs to mutation of core residues is plotted on a structural representation. The CD4bs is colored green, and tolerated point mutations are colored black, while substitutions driving reduced (<80%; light blue to red) or strongly enhanced (>160%; blue) binding to the core relative to WT are indicated. (B) Heatmap representation of the epitope-mapping results observed for the set of CD4bs mAbs. Hierarchical clustering identifies major subgroups of CD4bs mAbs that are associated with neutralization breadth and potency. The color bar at top indicates the class of core: core variants with substitutions made in CD4bs residues are indicated in green, core variants with substitutions made in other sites on the core indicated are indicated in black, and the unmutated WT core are indicated in gray. The color bar at the left indicates the mAb class, with bnAbs indicated in black and non-bnAbs indicated in shades of gray (vaccine-induced antibodies in light gray, infection-induced antibodies in dark gray).