The stoichiometry of binding between monoclonal antibody molecules and the hemagglutinin of influenza virus.
The number of neutralizing monoclonal IgG molecules that can bind to a single trimeric molecule of influenza viral hemagglutinin (HA) was calculated by estimating the molecular weight of the immune complexes formed under conditions of antibody excess and was found to be dependent upon the antigenic site to which the MAb is directed. Whereas three antibody molecules directed to site A or site E are able to bind simultaneously to a single trimer of HA, generally only one molecule directed to site B (the "tip") or site B/D ("tip/interface") can be accommodated. Using mixtures of MAbs, more IgG molecules can be accommodated, but steric hindrance limits simultaneous binding of different MAbs directed to the same antigenic site or even to neighboring sites. At limiting antibody concentration, some MAbs can form much larger aggregates in which several HA molecules are crosslinked by antibody. However, the fact that certain MAbs do not crosslink HA molecules in this way indicates that MAbs directed to different epitopes within the same general antigenic site differ significantly in their geometry of binding.
Poumbourios
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Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Brown
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White
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Jackson
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D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry; D000956:Antigens, Viral / Q000276:immunology; D001667:Binding, Competitive; D003196:Computer Graphics; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008970:Molecular Weight
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D000939:Epitopes; D006389:Hemagglutinins, Viral; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances