STRUCTURAL SIMILARITY OF ANTIBODY VARIABLE REGIONS FROM IMMUNE AND AUTOIMMUNE ANTI-DNA ANTIBODIES

Anti-DNA antibodies have been successfully induced in normal, nonautoi mmune mice by immunization with complexes formed with a DNA-binding pe ptide, Fus1, and native, B form, mammalian DNA. Fus1 is a 27-amino aci d peptide from the internal domain of a ubiquitin fusion protein from Trypanosoma cruzi. The structure of this peptide is homologous to the consensus amino acid sequence for a DNA-binding, ''zinc finger'' motif , and the peptide binds to DNA. A panel of six anti-DNA antibody-produ cing hybridomas, two IgM and four IgG2a, have been generated from a si ngle BALB/c mouse immunized with Fus1-DNA. The V region structures for both H and L chains of the induced anti-DNA antibodies are highly hom ologous if not identical to the V region structures of spontaneous ant i-DNA antibodies from autoimmune (NZB x NZW)F1 mice. The DNA specifici ties of the anti-DNA antibodies were also similar to those of autoimmu ne anti-DNA antibodies. Three of the four induced IgG antibodies bound equally well to native and denatured DNA. These results demonstrate t hat antibody specific for nDNA can be induced with immunogenic complex es of native DNA. They also demonstrate that monoclonal representative s of the induced anti-DNA antibodies have serologic and structural cha racteristics similar if not identical to those of spontaneous anti-DNA antibodies from autoimmune mice. The experimental system described he re should provide insight not only about the structural basis for auto immunity to DNA but also the function of anti-DNA antibody in the immu nopathology of SLE.