Induction of anti-DNA antibody with DNA-peptide complexes

Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibodies produced by antigen-specific, clonally selective B cell stim ulation. The nature of the somatically derived antibody variable region str uctures recurrent among spontaneous anti-DNA antibodies suggests that DNA o r DNA-protein complexes may provide the antigenic stimulus for autoimmune a nti-DNA antibody. Previously we have demonstrated that native mammalian DNA in complexes with an immunogenic DNA-binding peptide Fus1 from Trypanosoma cruzi can induce anti-DNA antibody in mice not genetically prone to autoim mune disease. The induced anti-DNA has similar specificity, structure and i mmunopathological function as autoimmune anti-DNA. The present experiments were designed to further characterize the immune response to DNA-peptide co mplexes. There was considerable variation in the antibody responses of mice from different strains to DNA-Fus1 immunizations. The range was from virtu ally no response in C57BL/6 mice to most robust responses in NZW mice. The full-length 52 amino acid carboxy-extension protein of ubiquitin (CEP) in T . cruzi (TCEP) protein from which Fus1 was derived functions equally well a s an immunogenic carrier for DNA. Anti-DNA responses were generally weak ev en though anti-Fus1 and anti-TCEP responses were very strong. The results a re discussed with respect to the contrasting roles of T cell help and perip heral B cell tolerance in controlling immune and autoimmune antibody respon ses to DNA.