HEAVY-CHAIN DOMINANCE IN THE BINDING OF DNA BY A LUPUS MOUSE MONOCLONAL AUTOANTIBODY

Antibodies H241 and 2C10 are lupus mouse IgG autoantibodies that bind native DNA. In previous experiments, oligonucleotide antigens affinity -labeled both H and L chains of H241 but only the H chain of antibody 2C10. Primary structures of the V regions of the 2C10 H and L chains a nd the H241 L chain, determined from cDNA, help to explain the previou s affinity-labeling experiments. The 2C10 L chain CDRs had several Asp residues and a net negative charge of five, whereas the 2C10 H chain CDRs had four Arg residues and a net positive charge of five. The L ch ain CDRs of H241 had a net positive charge of one. [The H241 H chain c DNA sequence was published previously by Gangemi ct al. (1993) J. Immu n. 151, 4660-4671]. Plasmid vectors were used for bacterial expression of H and L chains of 2C10 alone and in combinations in single chain F v (scFv) molecules. The H chain alone bound native DNA as well as or b etter than the H-plus-L chain scFv. The H chain alone also bound Z-DNA . Combination of the 2C10 H chain with the L chain of an anti-Z-DNA an tibody maintained the selectivity for Z-DNA, whereas its combination w ith the 2C10 L chain (in the 2C10 Fab) yielded selective B-DNA binding . The results with 2C10 match other examples in which the H chain is s ufficient for DNA binding but selectivity is modulated by the L chain. The H chain binding to autoantigen may reflect selective events in ea rly stages of B cell development.