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Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures

Schoppel, K. ; Haßfurther, E. ; Britt, W. ; Ohlin, M. LU orcid ; Borrebaeck, C. A K LU and Mach, M. (1996) In Virology 216(1). p.133-145
Abstract

Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all... (More)

Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all antibodies was observed with mutations at cysteine residues 573 and 610 as well as with a combinatorial exchange of prolines at position 577 and 613. The remaining mutations had different effects on antibody binding. Six individual recognition patterns were observed, indicating various antigenic substructures on AD-1. Changing the Fc portions of 3 murine monoclonal antibodies to human IgG1 showed that neutralization of AD-1-binding immunoglobulins is exerted by different mechanisms. Dependent on the recognized substructure within AD-1, avidity-dependent as well as Fc portion-mediated effects were observed.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
in
Virology
volume
216
issue
1
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:0342961137
  • pmid:8614980
ISSN
0042-6822
DOI
10.1006/viro.1996.0040
language
English
LU publication?
yes
id
3550c47f-d124-40d3-ace7-5037a623fbeb
date added to LUP
2016-04-19 14:15:05
date last changed
2024-03-06 19:41:19
@article{3550c47f-d124-40d3-ace7-5037a623fbeb,
  abstract     = {{<p>Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all antibodies was observed with mutations at cysteine residues 573 and 610 as well as with a combinatorial exchange of prolines at position 577 and 613. The remaining mutations had different effects on antibody binding. Six individual recognition patterns were observed, indicating various antigenic substructures on AD-1. Changing the Fc portions of 3 murine monoclonal antibodies to human IgG1 showed that neutralization of AD-1-binding immunoglobulins is exerted by different mechanisms. Dependent on the recognized substructure within AD-1, avidity-dependent as well as Fc portion-mediated effects were observed.</p>}},
  author       = {{Schoppel, K. and Haßfurther, E. and Britt, W. and Ohlin, M. and Borrebaeck, C. A K and Mach, M.}},
  issn         = {{0042-6822}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  pages        = {{133--145}},
  publisher    = {{Elsevier}},
  series       = {{Virology}},
  title        = {{Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures}},
  url          = {{http://dx.doi.org/10.1006/viro.1996.0040}},
  doi          = {{10.1006/viro.1996.0040}},
  volume       = {{216}},
  year         = {{1996}},
}