The targets and genes for antibodies to Z-DNA

Abstract

Antibodies to Z-DNA serve as models for recognition of nucleic acid structure by proteins that use peptide loops rather than helix-loop-helix, zinc-finger or other recurrent motifs for DNA binding. Anti-Z-DNA antibodies have been elicited in rabbits, mice and goats by injection of brominated poly(dG-dC), a stable form of Z-DNA. Detailed studies of two mouse monoclonal antibodies to Z-DNA, Z22 and Z44, have been reported. Epitopes on Z-DNA have been mapped by both serological reactions and n.m.r. spectroscopy. Antibodies Z22 and Z44 recognize different sites on the Z-DNA. They are both encoded by members of the VH10 gene family, which also encodes known autoantibodies to DNA. Vectors for bacterial expression of single-chain Fv molecules have been used to determine the importance of specific H- and L-chain combinations and particular CDR3 sequences for Z-DNA binding. Changes in the H-chain CDR3 cause a decrease in the highly selective Z-DNA binding and an increase in autoantibody-like binding of B-DNA and single-stranded DNA.