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Anti-DNA antibodies: aspects of structure and pathogenicity.

Authors
Jang, YJ; Stollar, BD
Citation
Cellular and molecular life sciences : CMLS, 60(2):309-320, 2003
Journal Title
Cellular and molecular life sciences : CMLS
ISSN
1420-682X1420-9071
Abstract
Anti-DNA antibodies contribute to the pathology of systemic lupus erythematosus. Their depositon in tissue lesions could result from localization of preformed immune complexes of antibodies with DNA or nucleosomes, or from cross-reaction of anti-DNA antibodies directly with tissue proteins. Structural analyses contribute to understanding their pathogenic potential. Primary structures of lupus immunoglobulin G double-stranded DNA-binding autoantibodies are determined by immunoglobulin genes with mutated variable region segments, indicative of selection by immunizing antigen. Arginine, lysine and asparagine residues in complementarity-determining region favor DNA binding. Heavy-chain variable regions make major contributions to DNA binding; affinity and specificity of binding are modulated or can be abrogated by the light-chain variable domain. Crytallographic structure is known for a few antibody-DNA complexes and several ligand-free Fab fragments. Computer modeling supplements this limited information. Structural information of lupus antibody interactions with both DNA and cross-reacting molecules will support use of ligands to inhibit tissue deposition of the antibodies and prevent lesion formation in lupus.
MeSH terms
AnimalsAntibodies, Antinuclear/chemistry*Antibodies, Antinuclear/geneticsAntibodies, Antinuclear/pharmacology*Antigen-Antibody Complex/metabolismComputer SimulationCrystallography, X-RayHumansImmunoglobulin G/geneticsImmunoglobulin G/immunologyImmunoglobulin Heavy Chains/chemistryImmunoglobulin Heavy Chains/metabolismImmunoglobulin Light Chains/metabolismImmunoglobulin Variable Region/chemistryImmunoglobulin Variable Region/geneticsImmunoglobulin Variable Region/immunologyImmunoglobulin Variable Region/metabolismLupus Erythematosus, Systemic/immunologyModels, MolecularMutation
PMID
12678496
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
장, 영주
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