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Heavy chain dominance in the binding of DNA by a lupus mouse monoclonal autoantibody.

Authors
Jang, YJ; Lecerf, JM; Stollar, BD
Citation
Molecular immunology, 33(2):197-210, 1996
Journal Title
Molecular immunology
ISSN
0161-58901872-9142
Abstract
Antibodies H241 and 2C10 are lupus mouse IgG autoantibodies that bind native DNA. In previous experiments, oligonucleotide antigens affinity-labeled both H and L chains of H241 but only the H chain of antibody 2C10. Primary structures of the V regions of the 2C10 H and L chains and the H241 L chain, determined from cDNA, help to explain the previous affinity-labeling experiments. The 2C10 L chain CDRs had several Asp residues and a net negative charge of five, whereas the 2C10 H chain CDRs had four Arg residues and a net positive charge of five. The L chain CDRs of H241 had a net positive charge of one. [The H241 H chain cDNA sequence was published previously by Gangemi et al. (1993) J. Immun. 151, 4660-4671]. Plasmid vectors were used for bacterial expression of H and L chains of 2C10 alone and in combinations in single chain Fv (scFv) molecules. The H chain alone bound native DNA as well as or better than the H-plus-L chain scFv. The H chain alone also bound Z-DNA. Combination of the 2C10 H chain with the L chain of an anti-Z-DNA antibody maintained the selectivity for Z-DNA, whereas its combination with the 2C10 L chain (in the 2C10 Fab) yielded selective B-DNA binding. The results with 2C10 match other examples in which the H chain is sufficient for DNA binding but selectivity is modulated by the L chain. The H chain binding to autoantigen may reflect selective events in early stages of B cell development.
MeSH terms
Amino Acid SequenceAnimalsAntibodies, Antinuclear/genetics/*metabolismAntibodies, Monoclonal/genetics/*metabolismB-Lymphocytes/immunologyBase SequenceCloning, MolecularDNA/*immunology/*metabolismDNA Primers/geneticsEscherichia coli/geneticsImmunoglobulin Fab Fragments/genetics/metabolismImmunoglobulin G/genetics/metabolismImmunoglobulin Heavy Chains/genetics/*metabolismImmunoglobulin Light Chains/genetics/metabolismImmunoglobulin Variable Region/genetics/metabolismLupus Erythematosus, Systemic/genetics/*immunology/metabolismMiceMolecular Sequence DataPolymerase Chain Reaction
PMID
8649441
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
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장, 영주
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