Biological activities of monoclonal antibodies reactive with antigenic sites mapped on the G1 glycoprotein of La Crosse virus.
Monoclonal antibodies have been prepared which are specific for the G1 glycoprotein of La Crosse virus. By competitive radioimmunoassay, 20 IgG-producing clones were found to map in eight antigenic sites; three distinct and five which showed individual patterns of partial competition indicating they may be in close proximity. Unique in situ trypsin cleavage sites on G1 have helped in orienting these defined epitopes relative to the viral membrane. Antibody molecules belonging to one epitope (H) mapped on the trypsin-resistant part of G1 and had negative or extremely low neutralizing and hemagglutination inhibition activities. Seven epitopes were located on the trypsin-sensitive part of G1, a 25,000-Da region which is probably the amino terminus of the protein. Antibodies binding to six of these seven epitopes (A, B, D, E, F, and G) were positive for neutralization and inhibition of hemagglutination, but exhibited a wide range of activities. Epitopes A, F, and G seem to be in an immunodominant region containing the primary site(s) for attachment to cell receptors. Antibody specific for the remaining epitope (C) was unique in that it bound to a site closely adjacent to neutralizing antibody sites, enhanced antibody binding to epitopes A and G, but lacked the capacity to neutralize viral infectivity or inhibit hemagglutination. Enhancement of antibody binding also occurred between two other closely adjacent sites (B and D) and one other distinct epitope (G). In addition, antibody from an IgM-producing clone competed with antibodies to these same four epitopes (B, C, D, and G), indicating they are in close proximity. These data have been used to construct an antigenic map that may now be used as a working model for the study of virus neutralization.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology*; D002043:Bunyaviridae / Q000276:immunology*; D002141:Encephalitis Virus, California / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006825:Hybridomas; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D014759:Viral Envelope Proteins