Ligand recognition by anti-DNA autoantibodies. Affinity, specificity, and mode of binding.
Understanding the molecular basis of DNA recognition by anti-DNA autoantibodies is a key element in defining the role of antibody.DNA complexes in the pathogenesis of the autoimmune disorder systemic lupus erythematosus. As part of our efforts to relate anti-DNA affinity and specificity to antibody structure, and ultimately to disease pathogenesis, we have generated a panel of eight anti-DNA mAbs from an autoimmune MRL MpJ-lpr/lpr mouse and have assessed the binding properties of these antibodies. We find that none of our anti-DNA mAbs bind to RNA and only one low-affinity mAb cross-reacts with non-DNA antigens, albeit weakly. None of the mAbs in our panel bind double-stranded DNA exclusively. Antibodies that recognize single-stranded DNA can be categorized into two groups based on their affinity and apparent mode of binding. One group possesses relatively high affinity for oligo(dT) and may recognize single-stranded DNA ligands by accommodating thymine bases in hydrophobic pockets on the antigen binding site. The second group binds more weakly, apparently recognizes single-stranded DNA nonspecifically, and in some cases also binds double-stranded DNA. Although different mechanisms are used for binding single- and double-stranded ligands, the mode of DNA recognition appears conserved within groups of antibodies.
Swanson
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PC
Department of Chemistry, University of Michigan, Ann Arbor 48109-1055, USA.
Ackroyd
C
C
Glick
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GD
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D001666:Binding Sites, Antibody; D004247:DNA / Q000276:immunology*; D018983:DNA Footprinting; D000939:Epitopes; D005260:Female; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000939:Epitopes; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D004247:DNA