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

Zhiyan Liang, Sooghee Chang, Min So Youn, Chandra Mohan

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.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.

Original languageEnglish (US)
Pages (from-to)2671-2681
Number of pages11
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 2009

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Nucleosomes
Chromatin
Anti-Idiotypic Antibodies
Autoantibodies
Antibodies
Congenic Mice
Immunoglobulin Heavy Chains
Chromosomes, Human, Pair 1
Molecular Structure
Aspartic Acid
Monoclonal Antibodies
Light

Keywords

  • Autoantibodies
  • Autoimmunity
  • B-cells
  • Genetics
  • Immunoglobulin repertoire

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1. / Liang, Zhiyan; Chang, Sooghee; Youn, Min So; Mohan, Chandra.

In: Molecular Immunology, Vol. 46, No. 13, 08.2009, p. 2671-2681.

Research output: Contribution to journalArticle

Liang, Zhiyan ; Chang, Sooghee ; Youn, Min So ; Mohan, Chandra. / Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1. In: Molecular Immunology. 2009 ; Vol. 46, No. 13. pp. 2671-2681.
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