Binding Characteristics Determine the Neutralizing Potential of Antibody Fragments Specific for Antigenic Domain 2 on Glycoprotein B of Human Cytomegalovirus

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Binding Characteristics Determine the Neutralizing Potential of Antibody Fragments Specific for Antigenic Domain 2 on Glycoprotein B of Human Cytomegalovirus. / Lantto, Johan; Fletcher, Jean M.; Ohlin, Mats.

I: Virology, Vol. 305, Nr. 1, 2003, s. 201-209.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Binding Characteristics Determine the Neutralizing Potential of Antibody Fragments Specific for Antigenic Domain 2 on Glycoprotein B of Human Cytomegalovirus

AU - Lantto, Johan

AU - Fletcher, Jean M.

AU - Ohlin, Mats

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1006/viro.2002.1752

DO - 10.1006/viro.2002.1752

M3 - Article

VL - 305

SP - 201

EP - 209

JO - Virology

JF - Virology

SN - 1096-0341

IS - 1

ER -