title: Epitopes of herpes simplex virus type 1 glycoprotein gC are clustered in two distinct antigenic sites.
abstract: Epitopes of herpes simplex virus type 1 (HSV-1) strain KOS glycoprotein gC were identified by using a panel of gC-specific, virus-neutralizing monoclonal antibodies and a series of antigenic variants selected for resistance to neutralization with individual members of the antibody panel. Variants that were resistant to neutralization and expressed an antigenically altered form of gC were designated monoclonal antibody-resistant (mar) mutants. mar mutants were isolated at frequencies of 10(-3) to 10(-5), depending on the antibody used for selection. The epitopes on gC were operationally grouped into antigenic sites by evaluating the patterns of neutralization observed when a panel of 22 antibodies was tested against 22 mar mutants. A minimum of nine epitopes was identified by this process. Three epitopes were assigned to one antigenic site (I), and six were clustered in a second complex site (II) composed of three distinct subsites, IIa, IIb, and IIc. The two antigenic sites were shown to reside in physically distinct domains of the glycoprotein, by radioimmunoprecipitation of truncated forms of gC. These polypeptides lacked portions of the carboxy terminus and ranged in size from approximately one-half that of the wild-type molecule to nearly full size. Antibodies recognizing epitopes in site II immunoprecipitated the entire series of truncated polypeptides and thereby demonstrated that site II resided in the N-terminal half of gC. Antibodies reactive with site I, however, did not immunoprecipitate fragments smaller than at least two-thirds the size of the wild-type polypeptide, suggesting that site I was located in the C-terminal portion. Sites I and II were also shown to be spatially separate on the gC polypeptide by competition enzyme-linked immunosorbent assay with monoclonal antibodies representative of different site I and site II epitopes.
authors.forename: S D
authors.initials: SD
authors.lastname: Marlin
authors.forename: T C
authors.initials: TC
authors.lastname: Holland
authors.forename: M
authors.initials: M
authors.lastname: Levine
authors.forename: J C
authors.initials: JC
authors.lastname: Glorioso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D002460:Cell Line; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000032:analysis*; D014644:Genetic Variation; D007668:Kidney; D007700:Kinetics; D008970:Molecular Weight; D009154:Mutation; D018139:Simplexvirus / Q000032:analysis* / Q000235:genetics; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000032:analysis* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C038535:glycoprotein gC, herpes simplex virus type 1