Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice

Harold Robert (Bob) III Bergen, M. J. Losman, T. O'Connor, W. Zacharias, J. E. Larson, M. A. Accavitti, R. D. Wells, W. J. Koopman

Research output: Contribution to journalArticle

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Abstract

Antibodies reactive with left-handed Z-DNA arise spontaneously in the sera of patients with SLE and rheumatoid arthritis and in autoimmune MRL mice. However, the precise specificity of these autoantibodies has not been established. In this report, we have characterized four monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice that do not cross-react with B-DNA and can discriminate between different types of left-handed helices. Two of the monoclonal antibodies (Za and Zi) behaved similarly in that they bound to two forms of Z-DNA (Br-poly(dG-dC)·poly(dG-dC) and AAF-poly(dG-dC)·poly(dG-dC)) but not to two other Z-form DNA (poly(dG-5BrdC)·poly(dG-5BrdC) or poly(dG-5-MedC)·poly(dG-5MedC)). Neither antibody (Za or Zi) bound significantly to B-DNA or to denatured DNA. A third antibody (Ze) exhibited similar binding characteristics for the Z-DNA preparations, but also recognized denatured DNA. In contrast, a fourth antibody (3-7.3) bound preferentially to poly(dG-5BrdC)·poly(dG-5BrdC) in Z conformation. These results provide the first evidence for anti-Z-DNA autoantibodies in autoimmune mice that do not cross-react with native or denatured DNA and indicate that these antibodies exhibit considerable heterogeneity in their fine binding specificity.

Original languageEnglish (US)
Pages (from-to)743-748
Number of pages6
JournalJournal of Immunology
Volume139
Issue number3
StatePublished - 1987
Externally publishedYes

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Z-Form DNA
Antinuclear Antibodies
Monoclonal Antibodies
Antibodies
B-Form DNA
Autoantibodies
DNA
Rheumatoid Arthritis
poly(dG)

ASJC Scopus subject areas

  • Immunology

Cite this

Bergen, H. R. B. III., Losman, M. J., O'Connor, T., Zacharias, W., Larson, J. E., Accavitti, M. A., ... Koopman, W. J. (1987). Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. Journal of Immunology, 139(3), 743-748.

Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. / Bergen, Harold Robert (Bob) III; Losman, M. J.; O'Connor, T.; Zacharias, W.; Larson, J. E.; Accavitti, M. A.; Wells, R. D.; Koopman, W. J.

In: Journal of Immunology, Vol. 139, No. 3, 1987, p. 743-748.

Research output: Contribution to journalArticle

Bergen, HRBIII, Losman, MJ, O'Connor, T, Zacharias, W, Larson, JE, Accavitti, MA, Wells, RD & Koopman, WJ 1987, 'Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice', Journal of Immunology, vol. 139, no. 3, pp. 743-748.
Bergen HRBIII, Losman MJ, O'Connor T, Zacharias W, Larson JE, Accavitti MA et al. Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. Journal of Immunology. 1987;139(3):743-748.
Bergen, Harold Robert (Bob) III ; Losman, M. J. ; O'Connor, T. ; Zacharias, W. ; Larson, J. E. ; Accavitti, M. A. ; Wells, R. D. ; Koopman, W. J. / Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. In: Journal of Immunology. 1987 ; Vol. 139, No. 3. pp. 743-748.
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abstract = "Antibodies reactive with left-handed Z-DNA arise spontaneously in the sera of patients with SLE and rheumatoid arthritis and in autoimmune MRL mice. However, the precise specificity of these autoantibodies has not been established. In this report, we have characterized four monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice that do not cross-react with B-DNA and can discriminate between different types of left-handed helices. Two of the monoclonal antibodies (Za and Zi) behaved similarly in that they bound to two forms of Z-DNA (Br-poly(dG-dC)·poly(dG-dC) and AAF-poly(dG-dC)·poly(dG-dC)) but not to two other Z-form DNA (poly(dG-5BrdC)·poly(dG-5BrdC) or poly(dG-5-MedC)·poly(dG-5MedC)). Neither antibody (Za or Zi) bound significantly to B-DNA or to denatured DNA. A third antibody (Ze) exhibited similar binding characteristics for the Z-DNA preparations, but also recognized denatured DNA. In contrast, a fourth antibody (3-7.3) bound preferentially to poly(dG-5BrdC)·poly(dG-5BrdC) in Z conformation. These results provide the first evidence for anti-Z-DNA autoantibodies in autoimmune mice that do not cross-react with native or denatured DNA and indicate that these antibodies exhibit considerable heterogeneity in their fine binding specificity.",
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AU - Bergen, Harold Robert (Bob) III

AU - Losman, M. J.

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AU - Zacharias, W.

AU - Larson, J. E.

AU - Accavitti, M. A.

AU - Wells, R. D.

AU - Koopman, W. J.

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N2 - Antibodies reactive with left-handed Z-DNA arise spontaneously in the sera of patients with SLE and rheumatoid arthritis and in autoimmune MRL mice. However, the precise specificity of these autoantibodies has not been established. In this report, we have characterized four monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice that do not cross-react with B-DNA and can discriminate between different types of left-handed helices. Two of the monoclonal antibodies (Za and Zi) behaved similarly in that they bound to two forms of Z-DNA (Br-poly(dG-dC)·poly(dG-dC) and AAF-poly(dG-dC)·poly(dG-dC)) but not to two other Z-form DNA (poly(dG-5BrdC)·poly(dG-5BrdC) or poly(dG-5-MedC)·poly(dG-5MedC)). Neither antibody (Za or Zi) bound significantly to B-DNA or to denatured DNA. A third antibody (Ze) exhibited similar binding characteristics for the Z-DNA preparations, but also recognized denatured DNA. In contrast, a fourth antibody (3-7.3) bound preferentially to poly(dG-5BrdC)·poly(dG-5BrdC) in Z conformation. These results provide the first evidence for anti-Z-DNA autoantibodies in autoimmune mice that do not cross-react with native or denatured DNA and indicate that these antibodies exhibit considerable heterogeneity in their fine binding specificity.

AB - Antibodies reactive with left-handed Z-DNA arise spontaneously in the sera of patients with SLE and rheumatoid arthritis and in autoimmune MRL mice. However, the precise specificity of these autoantibodies has not been established. In this report, we have characterized four monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice that do not cross-react with B-DNA and can discriminate between different types of left-handed helices. Two of the monoclonal antibodies (Za and Zi) behaved similarly in that they bound to two forms of Z-DNA (Br-poly(dG-dC)·poly(dG-dC) and AAF-poly(dG-dC)·poly(dG-dC)) but not to two other Z-form DNA (poly(dG-5BrdC)·poly(dG-5BrdC) or poly(dG-5-MedC)·poly(dG-5MedC)). Neither antibody (Za or Zi) bound significantly to B-DNA or to denatured DNA. A third antibody (Ze) exhibited similar binding characteristics for the Z-DNA preparations, but also recognized denatured DNA. In contrast, a fourth antibody (3-7.3) bound preferentially to poly(dG-5BrdC)·poly(dG-5BrdC) in Z conformation. These results provide the first evidence for anti-Z-DNA autoantibodies in autoimmune mice that do not cross-react with native or denatured DNA and indicate that these antibodies exhibit considerable heterogeneity in their fine binding specificity.

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