Sequence similarities among kappa IIIb chains of monoclonal human IgM kappa autoantibodies.
Light chains of the serologically and chemically defined V region sub-subgroup kappa IIIb are preferentially associated with several types of human IgM kappa (monoclonal) autoantibodies and are remarkably homologous in primary structure, as evidenced by partial amino acid sequence data. To establish the extent of homology among such proteins, we have determined the complete variable region (V) sequence of the light chains of four monoclonal IgM kappa autoantibodies, of which two (GAR and GOT) are rheumatoid factors (RFs), the third (SON) has anti-apo beta lipoprotein specificity, and the fourth (PIE) binds specifically to intermediate filaments. The region encoded by the V kappa segment gene (positions 1-95) in all four light (L) chains is virtually identical in sequence, differing by only one residue in the FR3 of protein SON and in the first CDR of protein GOT. Further, the CDR3 of kappa chain SON contains an additional residue (prolyl) located at the carboxyl-terminus of the V segment. The region encoded by the J gene (positions 96-108) is identical after position 96 for the two RFs GAR and GOT (J kappa 2), but different in proteins SON (J kappa 4) and PIE (J kappa 1). The amino acid residue at position 96, located in CDR3 at the site of combinatoriaL joining of the V kappa and J kappa gene segments and involved as a contacting residue in the hapten binding site, is different in all four light chains. These results demonstrate the extensive homology in sequence among light chains of IgM kappa autoantibodies and indicate that a particular V kappa germ line gene, kappa IIIb, is expressed as a phylogenetic response to certain self antigens or as part of a selection process by which these autoimmune responses are regulated.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000032:analysis; D000916:Antibody Diversity; D001323:Autoantibodies / Q000032:analysis; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008077:Lipoproteins, LDL / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis; D012217:Rheumatoid Factor / Q000032:analysis
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D012217:Rheumatoid Factor