Neutralizing monoclonal antibodies that distinguish three antigenic sites on human cytomegalovirus glycoprotein H have conformationally distinct binding sites.
Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map of two nonoverlapping antigenic sites that are bridged by a third antigenic site. Neutralization assays with 15 laboratory or clinical human cytomegalovirus strains indicated that the monoclonal antibodies recognize three antigenically variable and three conserved epitopes within the three antigenic sites. The variable-domain genes encoding monoclonal antibodies representing each of the three antigenic sites were cloned and sequenced, and molecular models of their binding sites were generated. Conformational differences in the antibody-binding sites suggested a structural basis for experimentally observed differences in gH epitope recognition.
Simpson
J A
JA
Protein Design Labs, Inc., Mountain View, California 94043.
Chow
J C
JC
Baker
J
J
Avdalovic
N
N
Yuan
S
S
Au
D
D
Co
M S
MS
Vasquez
M
M
Britt
W J
WJ
Coelingh
K L
KL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D000915:Antibody Affinity; D000918:Antibody Specificity; D001665:Binding Sites; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C044200:glycoprotein H, herpes simplex virus type 1