Anti-DNA antibodies bind to DNase I

Antonio Puccetti, Michael P. Madaio, Grazia Bellese, Paola Migliorini

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Polyspecificity is a well-known property of the anti-DNA antibodies produced by autoimmune animals. In our search for antigen targets of anti-DNA antibodies within tissue extracts, we identified a 32-kD polypeptide that was recognized by a large panel of anti-DNA antibodies. Direct sequencing of this protein disclosed its identity with DNase I. 22 monoclonal anti-DNA antibodies bound to DNase I in direct and competitive immunoassays; out of 15 autoantibodies that did not bind DNA, none had the ability to bind DNase I. The ability of anti-DNA antibodies to interfere with DNase I enzymatic activity was evaluated in an assay based on the enzyme digestion of phage double strand DNA. Six monoclonal anti-single strand DNA antibodies that did not bind double strand DNA were tested in this assay. Three out of six inhibited DNase I-mediated digestion of phage DNA. The interaction of anti-DNA antibodies with DNase I was further investigated by testing their ability to bind a synthetic peptide that corresponds to the catalytic site of the molecule. 4 out of 22 anti-DNA antibodies bound the active site peptide; two of these had been shown to inhibit DNase I enzymatic activity. This report shows that anti-DNA antibodies recognize both DNA and its natural ligand DNase I. Some anti-DNA antibodies inhibit DNase I enzymatic activity, thus displaying the potential to modulate DNA catabolism. The dual specificity of anti-DNA antibodies offers a clue for understanding the mechanisms that lead to anti-DNA antibody production in autoimmune animals.

Original languageEnglish (US)
Pages (from-to)1797-1804
Number of pages8
JournalJournal of Experimental Medicine
Volume181
Issue number5
DOIs
StatePublished - May 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Anti-DNA antibodies bind to DNase I'. Together they form a unique fingerprint.

  • Cite this

    Puccetti, A., Madaio, M. P., Bellese, G., & Migliorini, P. (1995). Anti-DNA antibodies bind to DNase I. Journal of Experimental Medicine, 181(5), 1797-1804. https://doi.org/10.1084/jem.181.5.1797