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 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.
Desai
D D
DD
Department of Microbiology and Immunology, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
Marion
T N
TN
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000918:Antibody Specificity / Q000235:genetics; D002645:Chickens; D016054:DNA, Protozoan / Q000276:immunology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D051381:Rats; D017422:Sequence Analysis, DNA; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear; D000913:Antibodies, Protozoan; D016054:DNA, Protozoan; D010455:Peptides; D011498:Protein Precursors; C499993:TUSC2 protein, human; D025521:Tumor Suppressor Proteins; C543627:Tusc2 protein, mouse; D014452:Ubiquitins; C045677:ubiquitin precursor