Lupus-derived autoantibodies with dual autoactivity: anti-DNA and anti-Fc. I. Comparison of IgG autoreactivities with single-chain Fv derivatives.
Investigations into the intrinsic affinity and reactivity of autoanti-DNA active sites were initiated through the use of purified monoclonal IgG and the synthesis of single-chain Fv derivatives of murine monoclonal anti-DNA autoantibodies BV 04-01 and BV 17-45. Results showed that relative to the respective IgG hybridomas, only the BV 04-01 SCA derivative showed demonstrable reactivity with DNA. The monovalent single-chain derivative of BV 17-45 showed no reactivity with DNA in solution or solid-phase assays, even though the parental IgG had been previously described as high affinity. However, 17-45 displayed reactivity as a bivalent single-chain derivative. In addition, upon concentration, BV 17-45 IgG formed a highly stable, papain-resistant precipitate. Investigations into the nature of the precipitate revealed that BV 17-45 possessed significant, DNA-inhibitable autobinding to its own IgG molecule. BV 04-01 also possessed similar anti-self reactivity. Thus, both monoclonal autoantibodies examined in this study possessed dual binding specificity; anti-DNa and anti-self.
Rumbley
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CA
Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA.
Voss
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D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D017931:DNA Primers; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; C055966:immunoglobulin Fv