This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McLinden, J. H.
Right arrow Articles by Stapleton, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McLinden, J. H.
Right arrow Articles by Stapleton, J. T.

 Previous Article  |  Next Article 

Journal of Virology, December 2006, p. 12131-12140, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01206-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Characterization of an Immunodominant Antigenic Site on GB Virus C Glycoprotein E2 That Is Involved in Cell Binding{triangledown}

James H. McLinden,1 Thomas M. Kaufman,1 Jinhua Xiang,1 Qing Chang,1 Donna Klinzman,1 Alfred M. Engel,2 Georg Hess,3 Urban Schmidt,2 Michael Houghton,4 and Jack T. Stapleton1*

Iowa City VA Medical Center and The University of Iowa, Iowa City, Iowa,1 Roche Diagnostics GmbH, Penzberg, Germany,2 Roche Diagnostics GmbH, Mannheim, Germany,3 Chiron Corporation, Emeryville, California4

Received 9 June 2006/ Accepted 28 September 2006

GB virus type C (GBV-C) is a human flavivirus that may cause persistent infection, although most infected individuals clear viremia and develop antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to topologically map immunogenic sites on GBV-C E2 and for the ability to detect or block recombinant E2 binding to various cell lines. Five competition groups of MAbs were identified. Groups I and II did not compete with each other. Group III competed with both groups I and II. Group IV did not compete with group I, II, or III. One MAb competed with all of the other MAbs, suggesting that the epitopes bound by these MAbs are intimately related. Individually, none of the MAbs competed extensively with polyclonal human convalescent antibody (PcAb); however, combinations of all five MAb groups completely blocked PcAb binding to E2, suggesting that the epitopes bound by these MAbs form a single, immunodominant antigenic site. Only group I and III MAbs detected purified recombinant E2 bound to cells in binding assays. In contrast, group II MAbs neutralized the binding of E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the peptide included four C-terminal or eight N-terminal residues, suggesting that the GBV-C E2 protein contains a single immunodominant antigenic site which includes a complex epitope that is involved in specific cellular binding.

* Corresponding author. Mailing address: Department of Internal Medicine, SW54, GH, The University of Iowa, Iowa City, IA 52242. Phone: (319) 356-3168. Fax: (319) 356-4600. E-mail: jack-stapleton{at}uiowa.edu.

{triangledown} Published ahead of print on 11 October 2006.

Journal of Virology, December 2006, p. 12131-12140, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01206-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»