Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype.
The NH2-terminal amino acid sequences have been determined by automated Edman degradation for the heavy and light chains of five monoclonal IgM anti-DNA autoantibodies that were produced by human-human hybridomas derived from lymphocytes of two patients with systemic lupus erythematosus. Four of the antibodies were closely related to the idiotype system 16/6, whereas the fifth antibody was unrelated idiotypically. The light chains of the 16/6 idiotype-positive autoantibodies (HF2-1/13b, HF2-1/17, HF2-18/2, and HF3-16/6) had identical amino acid sequences from residues 1 to 40. Their framework structures were characteristic of VKI light chains. The light chain of the 16/6 idiotype-negative autoantibody HF6-21/28 was characteristic of the VKII subgroup. The heavy chains of the 16/6 idiotype-positive autoantibodies had nearly identical amino acid sequences from residues 1 to 40. The framework structures were characteristic of the VHIII subgroup. In contrast, the GM4672 fusion partner of the hybridoma produced small quantities of an IgG with a VHI heavy chain and a VKI light chain. The heavy chains of the lupus autoantibodies and the light chains of those autoantibodies that were idiotypically related to the 16/6 system had marked sequence homology with WEA, a Waldenstrom IgM that binds to Klebsiella polysaccharides and expresses the 16/6 idiotype. These results indicate a striking homology in the amino termini of the heavy and light chains of the lupus autoantibodies studied and suggest that the V regions of the heavy and light chains of the 16/6 idiotype-positive DNA-binding lupus auto-antibodies are each encoded by a single germ line gene.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D001323:Autoantibodies / Q000032:analysis*; D004247:DNA / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000032:analysis*; D007075:Immunoglobulin M / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D004247:DNA