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Anti-DNA antibodies: aspects of structure and pathogenicity 总被引:4,自引:0,他引:4
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.
Received 4 July 2002; accepted 23 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
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Certain rheumatoid factors react with nucleosomes 总被引:16,自引:0,他引:16
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Dependence of Z-DNA antibody binding to polytene chromosomes on acid fixation and DNA torsional strain 总被引:1,自引:0,他引:1
There is considerable interest in the existence and significance of alternative conformations of DNA to the right-handed B-form described originally by Watson and Crick. The indirect immunofluorescence observations of Nordheim et al., Arndt-Jovin et al. and Lemeunier et al. that antibodies against left-handed Z-DNA bind to polytene chromosomes have thus assumed considerable importance. However, there is a paradox: some workers observe Z-DNA in interbands and others in bands. We report here that binding of Z-DNA antibodies to Drosophila polytene chromosomes prepared without acid fixation is at background level, and that following acid fixation the same antibody treatment leads to intense fluorescence. Depending on the extent of exposure to 45% acetic acid, fluorescence can occur primarily in interbands or in bands. Furthermore, antibody binding is dependent on elastic torsional strain in the DNA molecules. 相似文献
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Since its original development by Jerne, the haemolytic plaque assay has increased our understanding of antibody formation to a wide variety of antigens, including proteins, lipopolysaccharides, and simple haptens. We have now developed an assay to detect plaque forming cells (PFC) making anti-nucleoside antibodies. Previously we reported the suppression of circulating antibody to DNA determinants by nucleoside-IgG conjugates. Here we show that BALB/c mice can be rendered tolerant in terms of both direct and indirect anti-nucleoside antibody forming cells and that the state of tolerance is nucleoside-specific at the cellular level. 相似文献
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