Fine specificity and neutralizing activity of human serum antibodies directed to the major antigenic region on gp 116 of human cytomegalovirus

Silvestri, Michel; Jäderling, F.; Rudén, Ulla; Ohlin, Mats; Sundqvist, Vivi‐Anne

doi:10.1016/0888-0786(93)90004-j

Cited by 4 publications

(7 citation statements)

References 22 publications

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“…Synthetic peptides Peptides representing parts of AD‐2 were prepared according to 9‐fluorenylmethoxycarbonyl (Fmoc) chemistry as described previously [16]: T7‐11 (ANETIYNTTLKYGDV; amino acids 67–81 of gB, CMV AD169), T7‐13:3 (ETIYNTTLKY; amino acids 69–78 of gB) and T7‐13:7 (NTTLKYGDVV; amino acids 73–82 of gB). The following peptides were used as controls: P16 (TKLETNYTYI; scrambled sequence of T7‐13:3), P21 (YTLETYINKT; scrambled sequence of T7‐13:3), gH20 (AISEPLDKAFHLLLNT; amino acids 29–44 of gH, CMV Towne), gB51 (TVTSGSTKDT; amino acids 797–806 of gB, CMV AD169 [17]) and pp150:15 (LTPTPVNPSTAPAPAPTPTFAGTQTPVNGN; amino acids 594–623 of pp150 [18]).…”

Section: Methodsmentioning

confidence: 99%

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An Investigation into the Heparin‐Binding Properties of a Synthetic Peptide Deduced from the Antigenic Domain 2 of Human Cytomegalovirus Glycoprotein B

Silvestri

Sundqvist

2001

Scand J Immunol

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An investigation was performed into the heparin‐binding properties of a synthetic peptide deduced from the sequence of human cytomegalovirus glycoprotein B. The peptide, T7‐13:3, amino acids 69–78, which was previously shown to contain a neutralization epitope was able to bind heparin coated onto microtitre plates as well as immobilized on agarose beads. Conversely, labelled heparin could be used to specifically detect the immobilized peptide. The peptide bound to human cells in a manner which suggested an interaction with extracellular matrix, and binding of the peptide to human fibroblasts could be inhibited both by adding soluble heparin and by enzymatic pretreatment of the cells with heparinase. The sequence of T7‐13:3 shows similarity to several proteins with known or supposed ability to bind heparin, e.g. basic fibroblast growth factor, the heparin‐binding capacity of which could also be inhibited by T7‐13:3. The peptide was also found to bind DNA, probably due to the similarities between DNA and heparin in terms of structure and charge. Because heparin is a chemical homologue of heparan sulfate, the results strongly indicate that the sequence represented by T7‐13:3 is involved in the binding of virus to cell surface heparan sulfate. The described region of gB may have the potential to contribute to a subunit vaccine although possible hazards, such as the induction of auto‐antibodies to heparin, and thus also to DNA, need to be considered.

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Section: Methodsmentioning

confidence: 99%

“…The aim of this study was to show and characterize a putative ligand function within a short N‐terminal sequence of CMV gB that had previously been shown to contain a neutralization epitope [16].…”

Section: Introductionmentioning

confidence: 99%

An Investigation into the Heparin‐Binding Properties of a Synthetic Peptide Deduced from the Antigenic Domain 2 of Human Cytomegalovirus Glycoprotein B

Silvestri

Sundqvist

2001

Scand J Immunol

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“…The fine specificities of antibody repertoires specific for the AD-2 epitope that develop in vivo have only recently been investigated (12,16,23). Only two human monoclonal antibodies against this epitope have been described in any great detail, and they display very similar specificities in conventional analyses (12,16).…”

Section: Fig 2 Reactivity Of Human Gb (Ad-2)-specific Antibody Itc8mentioning

confidence: 99%

“…Only two human monoclonal antibodies against this epitope have been described in any great detail, and they display very similar specificities in conventional analyses (12,16). However, serum analysis using immobilized peptides as the antigen (23) suggests that some polyclonal antibody preparations contain AD-2-specific antibodies with slightly different reactivity patterns. Such screening tests can easily be performed by this ECL-based technique, and since the signal correlates in a linear fashion with the relative amount of bound antibody, the ultrafine specificity that develops following infection or vaccination can be efficiently determined.…”

Section: Fig 2 Reactivity Of Human Gb (Ad-2)-specific Antibody Itc8mentioning

confidence: 99%

“…Lately, both the fine specificity and the neutralizing capacity of various murine and human antibodies have been delineated (for a review, see reference 24). It has been established that these neutralization epitopes are actually composed of a series of overlapping subepitopes (21,23) and, at least in the case of AD-1, that only a fraction of the high-affinity antibodies against that epitope will actually mediate virus neutralization (21). Since gB is a molecule that has been investigated in various vaccine trials (1,6,17), it would be of value to efficiently monitor the developing humoral immunity repertoires against its epitopes.…”

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confidence: 99%

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Cytomegalovirus glycoprotein B-specific antibody analysis using electrochemiluminescence detection-based techniques

Ohlin

Silvestri

Sundqvist

et al. 1997

Clin Diagn Lab Immunol

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An electrochemiluminescence technique was used to develop versatile and sensitive assay strategies for determination of seroreactivities against biologically important cytomegalovirus neutralization epitopes expressed on glycoprotein B. Indirect binding assays showed wide linear assay ranges and revealed that serum samples diluted in parallel with a monoclonal antibody-based standard, simplifying quantitative analytical assessments.

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

2003

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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.

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Fine specificity and neutralizing activity of human serum antibodies directed to the major antigenic region on gp 116 of human cytomegalovirus

Cited by 4 publications

References 22 publications

An Investigation into the Heparin‐Binding Properties of a Synthetic Peptide Deduced from the Antigenic Domain 2 of Human Cytomegalovirus Glycoprotein B

An Investigation into the Heparin‐Binding Properties of a Synthetic Peptide Deduced from the Antigenic Domain 2 of Human Cytomegalovirus Glycoprotein B

Cytomegalovirus glycoprotein B-specific antibody analysis using electrochemiluminescence detection-based techniques

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

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