The neutralization site on the E2 glycoprotein of Venezuelan equine encephalomyelitis (TC-83) virus is composed of multiple conformationally stable epitopes.
The neutralization (N) site on the gp56 (E2) surface glycoprotein of the TC-83 vaccine strain of Venezuelan equine encephalomyelitis (VEE) virus has been characterized using monoclonal antibodies. Five new epitopes (E2d-h) were identified three of which could be mapped into the critical N site by using a competitive binding assay (CBA). Antibodies reactive with these three epitopes had either N or N and hemagglutination-inhibition activity. All epitopes contained within this N site elicited monoclonal antibodies that could protect mice from peripheral virus challenge. Antibodies reactive with the N site on other subtypes of VEE virus (IC and II) bound to, but failed to neutralize, TC-83 virus. Epitopes defined by these antibodies could be located outside of the N site on TC-83 virus by CBA. Antigenic activity of all epitopes except E2d was resistant to treatment with 2% SDS, 3% beta-mercaptoethanol, or cleavage with Staphylococcus aureus V8 protease. Those antibodies which defined epitopes located within the N site of TC-83 with CBA bound the same V8 fragments in immunoblots. Those antibodies which defined epitopes not located within the N site bound a different set of fragments than neutralizing antibodies. These results indicate that there is a specific N site on the E2 of VEE virus which undergoes significant antigenic drift while maintaining structural and functional integrity.
J T
JT
Roehrig
J H
JH
Mathews
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000936:Antigen-Antibody Complex; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007668:Kidney; D010954:Plasmacytoma / Q000276:immunology; D011487:Protein Conformation; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D014764:Viral Proteins