title: Binding characteristics determine the neutralizing potential of antibody fragments specific for antigenic domain 2 on glycoprotein B of human cytomegalovirus.
abstract: Site I of antigenic domain 2 (AD-2) on human cytomegalovirus glycoprotein B (gB) is poorly immunogenic in both man and mouse and knowledge about antibody repertoires reactive with this epitope is thus limited. Here we have characterized a phage display-derived repertoire of antibody fragments specific for this epitope in terms of antigen recognition, fine-specificity, and virus-neutralizing capacity. Our results show that the functional properties within a closely related repertoire may differ widely and that the effectiveness of the members of the repertoire to neutralize the virus is determined by the fine-specificity and kinetics of the interaction with the antigen. The half-life of the interaction between monomeric antibody fragments and gB seems to be particularly critical for the neutralizing capacity. We also demonstrate that sequence variation within gB allows virus variants to escape at least a part of the AD-2-specific neutralizing antibody repertoire, apparently without preventing antibody binding to the epitope.
authors.affiliation: Department of Immunotechnology, Lund University, S-220 07, Lund, Sweden
authors.forename: Johan
authors.initials: J
authors.lastname: Lantto
authors.forename: Jean M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Mats
authors.initials: M
authors.lastname: Ohlin
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007128:Immunoglobulin Fragments; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C055966:immunoglobulin Fv