Proteins of lymphocytic choriomeningitis virus: antigenic topography of the viral glycoproteins.
Topographical relationships among antigenic sites on the envelope glycoproteins of lymphocytic choriomeningitis virus (LCMV) were established using a panel of monoclonal antibodies (MAb) directed against viral GP-1 and GP-2. Purified MAb were radioiodinated and used as probes in a solid phase competitive binding assay. Epitopes on LCMV GP-1 were found to cluster in four antigenic sites. Five neutralizing MAb raised by immunization with the WE strain of LCMV reacted with a single topographic site, termed GP-1A, which was present on four strains of LCMV examined in this study. A second site, GP-1B, was characterized by two MAb which partially competed with one another and with a subset of neutralizing antibodies. This site appeared to be close to site A and was found to be nonneutralizing. The third site, GP-1C, contained sequential epitopes and was also nonneutralizing. Antibodies binding to site B enhanced the binding of MAb at site C, presumably through a conformational change. In addition to the common neutralizing site A, LCMV Armstrong strain (LCMV-Arm) GP-1 contained a second topographically related neutralizing site, GP-1D, which was specific for LCMV-Arm, absent in WE, and appeared to be the major immunogenic epitope on GP-1 of this virus. Analysis of MAb binding to LCMV GP-2 demonstrated the presence of three overlapping binding sites. GP-2A was defined by two antibodies while GP-2B and C represented binding sites of one antibody each. Guinea pigs primed with LCMV-Arm and challenged with LCMV-WE developed a significant immune response which was directed toward the common major neutralizing site, GP-1A, but had poor responses to the LCMV-Arm specific neutralizing site GP-1D. Immune sera contained antibody to site GP-1B but lacked detectable antibody to GP-1C.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000032:analysis* / Q000276:immunology; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000032:analysis; D006023:Glycoproteins / Q000276:immunology*; D006168:Guinea Pigs; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation; D051381:Rats; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D014764:Viral Proteins