Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures
(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.
(Less)
- author
- Schoppel, K. ; Haßfurther, E. ; Britt, W. ; Ohlin, M. LU ; Borrebaeck, C. A K LU and Mach, M.
- organization
- publishing date
- 1996-02-01
- 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
- 2024-05-16 23:59:37
@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}}, }