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      Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1

      , , ,
      Molecular Immunology
      Elsevier BV

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          Abstract

          Anti-nuclear antibodies constitute the hallmark of lupus. The NZM2410-derived Sle1 lupus susceptibility interval on murine chromosome 1 breaches tolerance, leading to the emergence of anti-nuclear autoantibodies targeting nucleosomes. However, little is known about the molecular structure of the anti-nucleosome autoantibodies from this genetically simplified mouse model of lupus. In this study, the immunoglobulin heavy chain and light chain sequences of 50 anti-nuclear monoclonal antibodies derived from five B6.Sle1(z) mice were compared to non-nuclear antibody controls. Compared to two different sets of non-nuclear antibodies, anti-nucleosome antibodies derived from B6.Sle1(z) congenic mice exhibited a high degree of clonal expansion and three distinct sequence motifs in their heavy chains - cationic CDR3 stretches, non-anionic CDR2 regions, and an increased frequency of aspartate residues at H50, which together increased the likelihood of an antibody being chromatin-reactive by approximately 4-fold.

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          Author and article information

          Journal
          Molecular Immunology
          Molecular Immunology
          Elsevier BV
          01615890
          August 2009
          August 2009
          : 46
          : 13
          : 2671-2681
          Article
          10.1016/j.molimm.2008.12.034
          2886130
          19556006
          d7135fba-562d-4a4b-8410-d60e8f8cb47c
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

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