Structural evidence for recognition of a single epitope by two distinct antibodies.
The structure of a complex between the hemagglutinin of influenza virus and the Fab of a neutralizing antibody was determined by X-ray crystallography at 2.8 A resolution. This antibody and another which has only 56% sequence identity bind to the same epitope with very similar affinities and in the same orientation. One third of the interactions is conserved in the two complexes; a significant proportion of the interactions that differ are established by residues of the H3 complementarity-determining regions (CDR) which adopt distinct conformations in the two antibodies. This demonstrates that there is a definite flexibility in the selection of antibodies that bind to a given epitope, despite the high affinity of their complexes. This flexibility allows the humoral immune response to be redundant, a feature that may be useful in achieving longer lasting protection against evolving viral pathogens.
Fleury
D
D
Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, France.
Daniels
R S
RS
Skehel
J J
JJ
Knossow
M
M
Bizebard
T
T
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry*; D000936:Antigen-Antibody Complex / Q000737:chemistry; D018360:Crystallography, X-Ray; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007140:Immunoglobulin Fab Fragments