TMP-reactive autoantibodies in human SLE sera demonstrate thymine-dependent oligonucleotide specificity.
Autoantibodies present in the sera of lupus patients and specific for single-stranded (ss) DNA were fractionated into subsets based upon their reactivity towards 5' nucleotide haptens. As evaluated by ELISA testing, antibodies retained by TMP-agarose bound to TMP-BSA and ssDNA but not to other nucleotide-BSA conjugates or to double-stranded (ds) DNA. Competition-inhibition studies further revealed that TMP-enriched oligo- and polynucleotides were the preferred antigens for these affinity purified antibodies. Similar assays with sequence- or size- defined oligonucleotides further implied that those oligonucleotides comprised entirely of TMP residues were most antigenic and that antigenicity increased with size (length). These results document the existence of a TMP-dependent oligonucleotide specificity among a diverse population of autoanti-ssDNA antibodies.
Munns
T W
TW
Washington University School of Medicine, Division of Rheumatology, St. Louis, MO 63110.
Freeman
S K
SK
D000974:Antibodies, Antinuclear / Q000032:analysis; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D013938:Thymidine Monophosphate / Q000276:immunology*; D013941:Thymine / Q000276:immunology / Q000502:physiology*; D013942:Thymine Nucleotides / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D000939:Epitopes; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate; D004247:DNA; D013941:Thymine