High-entropy epitope residues contribute to the strain specificity of 2C06 and 2C09
MUTANTS
While recognition of the 241 glycan hole explains much of the strain specificity of 2C06 and 2C09, there were seven strains other than BG505 in our 208-isolate panel missing glycan241, and we next investigated whether HIV sequence diversity of the epitope residues contributed to the strain-specific neutralization of these antibodies.We calculated the BSA-weighted average entropy of the epitope residues for fusion-peptide-directed antibodies as well as other broad HIV-neutralizing antibodies. We observed a negative correlation between epitope entropy and neutralization breadth for non-fusion peptide HIV-neutralizing antibodies (To identify epitope residues in BG505 that contribute to strain specificity, we analyzed Shannon entropy and BSA of epitope residues of 2C06 and 2C09 (To confirm the observed interactions of the epitope residues with substantial entropy, we mutated H85 or G644 in BG505 DS-SOSIP to the more frequent utilized amino acids among HIV-1 isolates and assessed the mutants for binding to 2C06 and 2C09 (Overall, the above analyses suggested that fusion-peptide-directed neutralizing antibodies elicited by BG505 Env immunization can partially accommodate the glycan hole at position 241. Those that do, however, encounter other BG505 strain-specific residues, proximal to fusion peptide, and their inability to accommodate variation at these other positions contributes to their strain specificity.