Specific recognition of a dsDNA sequence motif by an immunoglobulin VH homodimer

Anti-DNA antibodies have the potential to be applied in vast fields of fundamental as well as medical research. They are found in autoimmune diseases, such as systemic lupus erythemotosus. In most cases, anti-dsDNA antibodies do not present sequence specificity and are of low affinity. The dominant role of VH domains in DNA recognition induced us to search for binders based on VH dimers (VHD), previously reported to bind different protein antigens. We screened a phage displayed homo-VHD library against a 19-bp dsDNA sequence. A sequence-specific binder was selected, which recognizes the terminal located CTGC motif with a Kd of 250 nM. Association of the two identical VH domains of the molecule was shown to be essential for binding.