Light chain determines the binding property of human anti-dsDNA IgG autoantibodies.
We have previously prepared human anti-double-stranded (ds) DNA IgG Fab clones using phage-display technology. Nucleotide sequence analysis of genes of immunoglobulin (Ig) heavy and light chain variable regions in these Fab clones suggested that the DNA-binding activity of the clones depended on light chain usage. To confirm the role of the light chain in antibody binding to DNA, we constructed in the present study's new recombined Fab clones by heavy and light chain shuffling between the original anti-dsDNA Fab clones. Clones constructed by pairing Fdgamma fragments with the light chain from a high DNA-binding clone showed high DNA-binding activities, whereas other constructed clones using light chains from low DNA-binding clones showed low DNA-binding activities. Our results indicate that light chains in anti-dsDNA antibodies can determine the DNA-binding activity of the antibodies. Ig chain shuffling of phage-display antibodies may be useful for investigating the molecular mechanisms for antigen-antibody binding of human autoantibodies.
Suzuki
M
M
Division of Rheumatology, Department of Internal Medicine, Tsukuba-City, Ibaraki, 305-8575, Japan.
Takemura
H
H
Suzuki
H
H
Sumida
T
T
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D019151:Peptide Library
D001323:Autoantibodies; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D004247:DNA