A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site.
The structure of a complex of influenza hemagglutinin (HA) with a neutralizing antibody shows that the antibody binds to HA at a distance from the virus receptor binding site. Comparison of the properties of this antibody and its Fab with those of an antibody that recognizes an epitope overlapping the receptor binding site leads to two main conclusions. First, inhibition of receptor binding is an important component of neutralization. Second, the efficiency of neutralization by the antibodies ranks in the same order as their avidities for HA, and their large size makes these antibodies highly efficient at neutralization, regardless of the location of their epitope in relation to the virus receptor binding site. These observations provide rationales for the range of antibody specificities that are detected in immune sera and for the distribution of sequence changes on the membrane-distal surface of influenza HAs that occur during 'antigenic drift.'
Fleury
D
D
Laboratoire d'Enzymologie et Biochimie Structurales, UPR 9063, CNRS, Gif-sur-Yvette, France.
Barrère
B
B
Bizebard
T
T
Daniels
R S
RS
Skehel
J J
JJ
Knossow
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001665:Binding Sites; D002460:Cell Line; D003460:Crystallization; D018360:Crystallography, X-Ray; D004285:Dogs; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*
D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011991:Receptors, Virus