IgG anti-F(ab')2 antibodies from SLE patients react with immunodominant residues in kappa CDRs, but show reduced C kappa region reactivity.
We studied reactivity of affinity-purified human IgG anti-F(ab')2 antibodies for antigenic determinants on kappa light chains. Variable (VL) and constant (CL) regions of a human kappa I light chain (EU) were studied for enzyme-linked immunosorbent assay reactivity with monoclonal anti-k antibodies and human IgG antiF(ab')2 using overlapping heptamers of primary sequence synthesized as peptides on polypropylene pins. Polyclonal IgG anti-F(ab')2 antibodies isolated by affinity chromatography from the serum of patients with systemic lupus erythematosus (SLE) were found to react primarily with CDR1- and CDR3-related peptides. The most reactive residues included IL29, TRY32, LEU33, ALA34, GLU90, TYR91, and ASN 92. No striking difference in overall V-region anti-F(ab')2 reactivity profiles was noted when 10 IgG anti-F(ab')2 preparations from normal subjects and SLE patients were compared. In contrast, however, when tested against overlapping C kappa heptamer sequences, the reactivity in SLE-associated anti-F(ab')2 antibodies was markedly decreased. We report that this difference may reflect a defect in anti-idiotypic control mechanisms in SLE.
Williams
R C
RC
Department of Medicine, University of Florida Health Sciences Center, Gainesville 32610, USA.
Malone
C C
CC
Roemer
J H
JH
Silvestris
F
F
Solomon
A
A
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016056:Immunodominant Epitopes; D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains