Germline-encoded IgG antibodies bind mouse cartilage in vivo: epitope- and idiotype-specific binding and inhibition.
Autoantibodies specific for type-II collagen (CII) occur in mice and rats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found that antibodies binding to the same epitope in CII in vivo can inhibit others from binding in an epitope-specific fashion. The binding in vivo and in vitro of anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum produced against the D3 antibody. The anti-idiotypic antiserum inhibited the binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without somatic mutations. The variable heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming that they share idiotypes. This report demonstrates that CII-specific germline-encoded IgG autoantibodies bind specifically to normal cartilage in vivo via their combining site.
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Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Scheynius
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Nilsson
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Holmdahl
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R
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D001666:Binding Sites, Antibody; D002358:Cartilage, Articular / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D003094:Collagen