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

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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.

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  1. Penn Center for Molecular Studies of Kidney Diseases Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, 700 Clinical Research Building, 19104-6144, Philadelphia, PA, (USA)

    Mary H. Foster, Michael Ohliger & Michael P. Madaio

  2. Wistar Institute of Biology and Anatomy, Philadelphia, Pa., USA

    Thomas Kieber-Emmons

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  1. Mary H. Foster
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  2. Thomas Kieber-Emmons
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  3. Michael Ohliger
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  4. Michael P. Madaio
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Foster, M.H., Kieber-Emmons, T., Ohliger, M. et al. Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies. Immunol Res 13, 186–206 (1994). https://doi.org/10.1007/BF02918279

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