Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies.
Anti-DNA antibodies have been successfully induced in normal, nonautoimmune mice by immunization with complexes formed with a DNA-binding peptide, Fus1, and native, B form, mammalian DNA. Fus1 is a 27-amino acid 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-producing hybridomas, two IgM and four IgG2a, have been generated from a single 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 homologous if not identical to the V region structures of spontaneous anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. The DNA specificities of the anti-DNA antibodies were also similar to those of autoimmune anti-DNA antibodies. Three of the four induced IgG antibodies bound equally well to native and denatured DNA. These results demonstrate that antibody specific for nDNA can be induced with immunogenic complexes of native DNA. They also demonstrate that monoclonal representatives of the induced anti-DNA antibodies have serologic and structural characteristics similar if not identical to those of spontaneous anti-DNA antibodies from autoimmune mice. The experimental system described here should provide insight not only about the structural basis for autoimmunity to DNA but also the function of anti-DNA antibody in the immunopathology of SLE.
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
M R
MR
Krishnan
T N
TN
Marion
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry* / Q000235:genetics; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000276:immunology; D001483:Base Sequence; D001666:Binding Sites, Antibody; D004247:DNA / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000974:Antibodies, Antinuclear; D007135:Immunoglobulin Variable Region; D004247:DNA