Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies

Mary H. Foster, Thomas Kieber-Emmons, Michael Ohliger, Michael P. Madaio

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig.

Original languageEnglish (US)
Pages (from-to)186-206
Number of pages21
JournalImmunologic Research
Volume13
Issue number2-3
DOIs
StatePublished - Jun 1 1994

Keywords

  • Anti-DNA
  • Antibody modeling
  • Autoantibodies
  • Lupus
  • Nuclear localization
  • Tertiary conformation
  • V genes, variable-region genes

ASJC Scopus subject areas

  • Immunology

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    Foster, M. H., Kieber-Emmons, T., Ohliger, M., & Madaio, M. P. (1994). Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies. Immunologic Research, 13(2-3), 186-206. https://doi.org/10.1007/BF02918279