Ligand recognition by anti-DNA autoantibodies. Affinity, specificity, and mode of binding

Patrick Swanson, Christine Ackroyd, Gary D. Glick

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Understanding the molecular basis of DNA recognition by anti-DNA autoantibodies is a key element in defining the role of antibody·DNA complexes in the pathogenesis of the autoimmune disorder systemic lupus erythematosus. As part of our efforts to relate anti-DNA affinity and specificity to antibody structure, and ultimately to disease pathogenesis, we have generated a panel of eight anti-DNA mAbs from an autoimmune MRL MpJ- lpr/lpr mouse and have assessed the binding properties of these antibodies. We find that none of our anti-DNA mAbs bind to RNA and only one low-affinity mAb cross-reacts with non-DNA antigens, albeit weakly. None of the mAbs in our panel bind double-stranded DNA exclusively. Antibodies that recognize single-stranded DNA can be categorized into two groups based on their affinity and apparent mode of binding. One group possesses relatively high affinity for oligo(dT) and may recognize single-stranded DNA ligands by accommodating thymine bases in hydrophobic pockets on the antigen binding site. The second group binds more weakly, apparently recognizes single- stranded DNA nonspecifically, and in some cases also binds double-stranded DNA. Although different mechanisms are used for binding single- and double- stranded ligands, the mode of DNA recognition appears conserved within groups of antibodies.

Original languageEnglish
Pages (from-to)1624-1633
Number of pages10
JournalBiochemistry
Volume35
Issue number5
DOIs
StatePublished - Feb 6 1996
Externally publishedYes

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Autoantibodies
Ligands
DNA
Single-Stranded DNA
Antibodies
Antigens
Thymine
Antibody Specificity
Systemic Lupus Erythematosus
Binding Sites
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Ligand recognition by anti-DNA autoantibodies. Affinity, specificity, and mode of binding. / Swanson, Patrick; Ackroyd, Christine; Glick, Gary D.

In: Biochemistry, Vol. 35, No. 5, 06.02.1996, p. 1624-1633.

Research output: Contribution to journalArticle

Swanson, Patrick ; Ackroyd, Christine ; Glick, Gary D. / Ligand recognition by anti-DNA autoantibodies. Affinity, specificity, and mode of binding. In: Biochemistry. 1996 ; Vol. 35, No. 5. pp. 1624-1633.
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