SELECTION OF RECURRENT V-GENES AND SOMATIC MUTATIONS IN AUTOANTIBODIES TO DNA

Antigen selection of autoantibodies to DNA results in the use of limit ed sets of immunoglobulin heavy and light chains, characteristic VDJ a nd VJ joining regions, and recurrent patterns of somatic mutations. In the past, we have used site-directed mutagenesis to examine the roles of two recurrent features of anti-DNA antibodies: VHCDR3 arginine and somatic mutations to arginine. We observed that in one prototypic ant i-DNA antibody, 3H9, a suitable CDR3 conformation is essential for DNA binding and depends on arginine. In addition, arginines at any of fiv e positions in CDR1, CDR2, or FWR3 of the heavy chain contribute conta cts with the antigen. Here, we extend these studies and report that ar ginines at positions 52 and 58 improve relative DNA binding but that b inding critically depends on the germline-encoded arginine at position 50. These observations provide a more detailed view of the anti-DNA c ombining site and suggest that structural features account, at least i n part, for the recurrence of heavy chain variable regions in anti-DNA antibodies. (C) 1997 Academic Press, Inc.