Characterization of neutralizing monoclonal antibodies to murine cytomegalovirus.
Monoclonal antibodies (MAbs) and polyclonal antibodies raised in mice to murine cytomegalovirus (MCMV) were characterized in vitro by their virus-neutralizing activity and their reactivity with MCMV polypeptides and MCMV-infected mouse embryo fibroblasts (MEF). MCMV was neutralized by the MAbs prior to virus adsorption to MEF by a complement-dependent mechanism. Although the neutralization of MCMV prior to virus adsorption to MEF by polyclonal antibodies was enhanced in the presence of complement, MCMV was also neutralized by a complement-independent mechanism after virus adsorption. No correlation was observed between the level of neutralization of MCMV and the ability of MAbs or polyclonal antibodies to interfere with the binding of the virus to MEF. As the neutralization of MCMV with polyclonal antibodies by both complement-dependent and -independent mechanisms may reflect the interaction of antibodies with different specificities, the ability of each MAb to interact with a second MAb was investigated. One MAb, 1E8, inhibited the neutralizing activity of several other MAbs. Several MAbs reacted with multiple polypeptides by immunoprecipitation and Western blotting analysis; MAb AC1 cross-reacted with a neutralizing 92K/98K MCMV domain and a 70K ribonucleoprotein, the latter with which sera from patients with connective tissue diseases also reacted. This suggests that an homology exists between these proteins, which may lead to the development of autoimmune manifestations in vivo.
Farrell
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HE
Department of Microbiology, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
Shellam
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GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral / Q000276:immunology; D015153:Blotting, Western; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007136:Immunoglobulins / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D007136:Immunoglobulins