Characterization of an immunodominant antigenic site on GB virus C glycoprotein E2 that is involved in cell binding.
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.
McLinden
James H
JH
Department of Internal Medicine, SW54, GH, The University of Iowa, Iowa City, IA 52242, USA.
Kaufman
Thomas M
TM
Xiang
Jinhua
J
Chang
Qing
Q
Klinzman
Donna
D
Engel
Alfred M
AM
Hess
Georg
G
Schmidt
Urban
U
Houghton
Michael
M
Stapleton
Jack T
JT
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000235:genetics*; D002460:Cell Line; D018604:Epitope Mapping; D029407:GB virus C / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D014759:Viral Envelope Proteins / Q000235:genetics*; D053585:Virus Attachment
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins