title: The role of monogamous bivalency and Fc interactions in the binding of anti-DNA antibodies to DNA antigen.
abstract: Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus. These antibodies can bind DNA avidly by monogamous bivalency, a mechanism which requires the interaction of both Fab combining regions with antigenic determinants on the same polynucleotide. To explore further this mechanism, we tested Fab and F(ab')2 fragments prepared from IgG from patient plasmas in an ELISA with native DNA antigen, detecting antibody with a peroxidase conjugated anti-Fab reagent. These studies showed that Fab fragments, which can only bind monovalently, had negligible activity. Although bivalent F(ab')2 fragments would be predicted to bind DNA, these fragments also showed poor anti-DNA activity. Control studies showed that the fragments retained antibody activity to tetanus toxoid and an EBV antigen preparation. Together, these findings suggest that anti-DNA avidity depends on monogamous bivalency, with the antibody Fc portion also influencing DNA binding, in a mechanism which can be termed Fc-dependent monogamous bivalency.
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Medical Research Service, VA Medical Center, Durham, NC, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Stearns
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Medical Research Service, VA Medical Center, Durham, NC, USA. Electronic address: david.pisetsky@duke.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Pisetsky
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000956:Antigens, Viral; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D004247:DNA
keywords: Anti-DNA; Avidity; ELISA; Monogamous bivalency; Systemic lupus erythematosus