Analysis of three new idiotypes on human monoclonal autoantibodies

The base pairs in double helical nucleic acids have been compared to see how they can be recognized by proteins. We conclude that a single hydrogen bond is inadequate for uniquely identifying any particular base pair, as this leads to numerous degeneracies. However, using two hydrogen bonds, fidelity of base pair recognition may be achieved. We propose specific amino-acid side chain interactions involving two hydrogen bonds as a component of the recognition system for base pairs. In the major groove we suggest that asparagine or glutamine binds to adenine of the base pair or arginine binds to guanine. In the minor groove, we suggest an interaction between asparagine or glutamine with guanine of the base pair. We also discuss the role that ions and other amino-acid side chains may play in recognition interactions.

The primary structure of anti-DNA antibodies is highly diverse, a result of different germline variable (V) gene use, different combinations of immunoglobulin gene segments, peculiar heavy chain complementarity determining region 3 (H-CDR3) segments, and somatic mutations. Nevertheless, tertiary structure predictions reveal common features that yield information about likely contact sites in the anti-DNA combining site. That these contacts are involved with DNA binding is supported by recurrent features of a newly compiled set of homology groups of 13 variable regions of heavy chains (VH) and 11 variable regions of light chains (VL), characteristic pattern of somatic mutations, and the results of site-directed mutagenesis. The role of antigen in the etiology of the autoimmune response is viewed in light of recent data on overlaps between anti-DNA and anti-nucleic acid binding protein specificities.