GENETIC AND STRUCTURAL EVIDENCE FOR ANTIGEN SELECTION OF ANTI-DNA ANTIBODIES

The primary structure of anti-DNA antibodies is highly diverse, a resu lt 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. Nevert heless, tertiary structure predictions reveal common features that yie ld information about likely contact sites in the anti-DNA combining si te. That these contacts are involved with DNA binding is supported by recurrent features of a newly compiled set of homology groups of 13 va riable regions of heavy chains (V-H) and 11 variable regions of light chains (V-L), characteristic pattern of somatic mutations, and the res ults of site-directed mutagenesis. The role of antigen in the etiology of the autoimmune response is viewed in light of recent data on overl aps between anti-DNA and anti-nucleic acid binding protein specificiti es.