Selection of recurrent V genes and somatic mutations in autoantibodies to DNA

Marko Radic, Samarendra N. Seal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Antigen selection of autoantibodies to DNA results in the use of limited sets of immunoglobulin heavy and light chains, characteristic VDJ and 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 anti-DNA antibody, 3H9, a suitable CDR3 conformation is essential for DNA binding and depends on arginine. In addition, arginines at any of five positions in CDR1, CDR2, or FWR3 of the heavy chain contribute contacts with the antigen. Here, we extend these studies and report that arginines at positions 52 and 58 improve relative DNA binding but that binding critically depends on the germline-encoded arginine at position 50. These observations provide a more detailed view of the anti-DNA combining site and suggest that structural features account, at least in part, for the recurrence of heavy chain variable regions in anti-DNA antibodies.

Original languageEnglish (US)
Pages (from-to)20-26
Number of pages7
JournalMethods: A Companion to Methods in Enzymology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1997

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Autoantibodies
Arginine
Genes
Mutation
Antinuclear Antibodies
DNA
Immunoglobulin Light Chains
Antigens
Immunoglobulin Heavy Chains
Mutagenesis
Site-Directed Mutagenesis
Joining
Conformations
Binding Sites
Recurrence

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Selection of recurrent V genes and somatic mutations in autoantibodies to DNA. / Radic, Marko; Seal, Samarendra N.

In: Methods: A Companion to Methods in Enzymology, Vol. 11, No. 1, 01.01.1997, p. 20-26.

Research output: Contribution to journalArticle

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