Figure 7. Locality of mutations required for gain of function.

Summary of the location of mutations critical for acquiring binding and activity functions in all five ADCC Ab lineages, respective to the previous step, that is building upon one another to gain functions. Lineages are summarized by row. Detectable ADCC function excludes lineage members with indeterminate ADCC activity, as defined in Materials and methods. Augmented ADCC activity indicates lineage members with activity most comparable to that of their respective mature. *157-0_VHA_VK required mutations for function while 157-0_VH0_VK did not; Env binding and detectable ADCC determinants were defined based on this comparison. fnl: functional. See Figure 7—figure supplement 1 for a more detailed summary graphic of key steps to attain function in all six lineages.

Figure 7—figure supplement 1. Key steps in ADCC development among six lineages.

Graphic summaries of development for each antibody lineage. Antibodies (ovals) are arranged from naïve (top) to mature (bottom) with inferred intermediates in between, colored by ADCC functionality: no function or indeterminate (gray), low function (<50% of mature activity; light blue), high function (>50% of mature activity; dark blue). Arcs connecting ovals indicate amino acid substitutions in the heavy chain (left) and light chain (right), colored by their locality: CDR (yellow), FWR (blue), both (green), or no change (gray, thin). The red outline within the 016 lineage denotes that the light chain mutation is an insertion, not a substitution. The blue outline within the 105 lineage denotes the presence of a FR4 mutation that was likely a computational artifact, since this position backmutates within the mature antibody.