کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2831409 | 1163804 | 2009 | 11 صفحه PDF | دانلود رایگان |
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.Sle1z mice were compared to non-nuclear antibody controls. Compared to two different sets of non-nuclear antibodies, anti-nucleosome antibodies derived from B6.Sle1z 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 ∼4-fold.
Journal: Molecular Immunology - Volume 46, Issue 13, August 2009, Pages 2671–2681