title: Structural properties of a subset of nephritogenic anti-DNA antibodies.
abstract: Structural analysis of lupus autoantibodies is beginning to provide clues to the molecular basis for antigenic specificity and pathogenicity. The present analysis indicates that multiple light and heavy chains contain residues which can facilitate DNA binding, reaffirming the notion that there are multiple ways that different amino acids combine to form an antigen-binding pocket with affinity for dsDNA and ssDNA. Furthermore, this analysis suggests that these conformations and contact residues are intrinsic to germline sequences, although amino acid changes at critical locations (somatically introduced) modulate antigen binding, and appear to influence the capacity of individual immunoglobulin to form immune deposits. Analysis of additional individual immunoglobulins with closely related V-region sequences and differing pathogenic properties will be required to resolve the contribution of specific motifs to pathogenecity.
authors.affiliation: Wistar Institute of Biology and Anatomy, University of Pennsylvania, Philadelphia, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kieber-Emmons
authors.forename: M H
authors.initials: MH
authors.lastname: Foster
authors.forename: W V
authors.initials: WV
authors.lastname: Williams
authors.forename: M P
authors.initials: MP
authors.lastname: Madaio
mesh_terms: D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region