Anti-DNA antibodies bind to DNase I

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Deoxyribonuclease I
Antinuclear Antibodies
DNA
Bacteriophages
Peptides
Digestion
Catalytic Domain
Tissue Extracts
Protein Sequence Analysis
Immunoassay
Autoantibodies
Antibody Formation
Monoclonal Antibodies
Ligands
Antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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

Anti-DNA antibodies bind to DNase I. / Puccetti, Antonio; Madaio, Michael P.; Bellese, Grazia; Migliorini, Paola.

In: Journal of Experimental Medicine, Vol. 181, No. 5, 01.05.1995, p. 1797-1804.

Research output: Contribution to journalArticle

Puccetti, A, Madaio, MP, Bellese, G & Migliorini, P 1995, 'Anti-DNA antibodies bind to DNase I', Journal of Experimental Medicine, vol. 181, no. 5, pp. 1797-1804. https://doi.org/10.1084/jem.181.5.1797
Puccetti A, Madaio MP, Bellese G, Migliorini P. Anti-DNA antibodies bind to DNase I. Journal of Experimental Medicine. 1995 May 1;181(5):1797-1804. https://doi.org/10.1084/jem.181.5.1797
Puccetti, Antonio ; Madaio, Michael P. ; Bellese, Grazia ; Migliorini, Paola. / Anti-DNA antibodies bind to DNase I. In: Journal of Experimental Medicine. 1995 ; Vol. 181, No. 5. pp. 1797-1804.
@article{f34c3f4ff4ff4c09a7d4b7b856b20c26,
title = "Anti-DNA antibodies bind to DNase I",
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.",
author = "Antonio Puccetti and Madaio, {Michael P.} and Grazia Bellese and Paola Migliorini",
year = "1995",
month = "5",
day = "1",
doi = "10.1084/jem.181.5.1797",
language = "English (US)",
volume = "181",
pages = "1797--1804",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Anti-DNA antibodies bind to DNase I

AU - Puccetti, Antonio

AU - Madaio, Michael P.

AU - Bellese, Grazia

AU - Migliorini, Paola

PY - 1995/5/1

Y1 - 1995/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028952166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028952166&partnerID=8YFLogxK

U2 - 10.1084/jem.181.5.1797

DO - 10.1084/jem.181.5.1797

M3 - Article

C2 - 7722456

AN - SCOPUS:0028952166

VL - 181

SP - 1797

EP - 1804

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -