Influenza HA antigenic sites. (a) Comparison of previously described antigenic sites in influenza H1 H3, or B HA. For each HA, the structure to the left shows the previously defined antigenic site residues mapped onto a monomer an appropriate crystal structure, while the structure on the right shows residues colored according to the frequency of absolute change (i.e. any amino acid substituted with any other) in comparison with the same residue in the most closely related sequence (abs, see Materials and Methods, color code shown in panel b), viewed from the top (T) or side (S). The H1 structure shows antigenic residues  mapped onto the 3D structure of A/Puerto Rico/8/24 HA (PR8, PDB ID: 1RU7). Color scheme for antigenic sites: Ca1, olive; Ca2, blue; Sb, yellow; Sa, orange; Cb, red, as indicated by labels on the structure. Neutralizing antigenic sites  of influenza A H3 HA monomer mapped onto the crystal structure of A/X-31 HA (PBD ID: 2VIU). Color scheme: antigenic site A, blue; B, yellow; C, red; D, orange; E, magenta Antigenic sites in influenza B HA  mapped onto the 3D structure of B/Lee/40 HA (PDB ID: 1RFT), viewed from the top (T) or side (S). Color scheme: antigenic site A, blue; B, yellow; c, red; D, orange; E, magenta; base of receptor binding pocket, purple. (b) Color scheme indicating frequency of change: frequency below 50th percentile of all residues in HA1, white; between 50th and 75th percentile, green; between 75th and 90th percentile, orange; 90th percentile and above, red. (c). Views of H1, H3, and influenza B HA monomers from behind. (d) Crystal structure of H3 HA trimer (PBD ID: 2VIU), viewed from the top, the side, and along the intratrimer axis, shown for orientation.