Identification and sequence of the VH gene elements encoding a human anti-DNA antibody

Antibodies to DNA similar to those found in patients with systemic lupus erythematosus (SLE) and autoimmune mice can be derived from the lymphocytes of normal individuals. It is not known whether these normal derived anti-DNA antibodies are made from the same VH gene elements as the anti-DNA antibodies made by SLE patients. To begin to answer this question, we examined mu chain cDNA clones from human hybrid clone C6B2 producing anti-DNA antibodies. The sequence of the 500 base pair restriction fragment containing the variable region (5' terminus) was determined and was sequenced. This antibody uses a VHII heavy chain subgroup gene, a J3 joining segment, a hitherto unknown D segment, and a previously reported leader sequence. Significant homology was found to a mouse anti-DNA antibody sequence in the use of VH subgroup in J3, and in the hypervariable regions with a shared Ser-Tyr construction in CDR1 and an identical five amino acid residue stretch in CDR2. Comparison with the limited sequence data of published SLE monoclonal anti-DNA antibodies, both human and mouse, suggests that this shared Ser-Tyr may be important in some but not all antibodies to DNA. Comparison of C6B2 antibody is made with other known antibody sequences with identification of those residues likely to be part of the antigen binding site.