Induction of anti-DNA antibody with DNA–peptide complexes

• Published in: International immunology 2000-11, Vol.12 (11), p.1569-1578
• Main Authors: Desai, Dharmesh D., Marion, Tony N.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; anti-DNA antibodies; Antibodies, Antinuclear - biosynthesis; Antibodies, Protozoan - biosynthesis; Antibody Specificity - genetics; antinuclear antibodies; autoimmunity; Chickens; DNA, Protozoan - immunology; Female; Fus1 peptide derived from an internal amino acid sequence of CEP; Humans; immunization; mFus1 mouse homologue of Fus1; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred NZB; Molecular Sequence Data; nDNA native DNA; Peptides - genetics; Peptides - immunology; Protein Precursors - genetics; Protein Precursors - immunology; Rats; Sequence Analysis, DNA; TCEP ubiquitin carboxy extension protein from T. cruzi; tolerance; Trypanosoma cruzi - genetics; Trypanosoma cruzi - immunology; Tumor Cells, Cultured; Tumor Suppressor Proteins; ubiquitin; Ubiquitins - genetics; Ubiquitins - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/12.11.1569

Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibodies produced by antigen-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody variable region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA–protein complexes may provide the antigenic stimulus for autoimmune anti-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 autoimmune disease. The induced anti-DNA has similar specificity, structure and immunopathological function as autoimmune anti-DNA. The present experiments were designed to further characterize the immune response to DNA–peptide complexes. There was considerable variation in the antibody responses of mice from different strains to DNA–Fus1 immunizations. The range was from virtually 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 as an immunogenic carrier for DNA. Anti-DNA responses were generally weak even though anti-Fus1 and anti-TCEP responses were very strong. The results are discussed with respect to the contrasting roles of T cell help and peripheral B cell tolerance in controlling immune and autoimmune antibody responses to DNA.