Secondary Structure in Denatured DNA is Responsible for Its Reaction with Antinative DNA Antibodies of Systemic Lupus Erythematosus Sera

Stollar, B D; Papalian, Michael M.

doi:10.1172/jci109846

Cited by 61 publications

(13 citation statements)

References 33 publications

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“…Either double-stranded polynucleotides or denatured DNA effectively compete with these antibodies for native DNA binding (24, 25, 28-30). These immunoglobulins may interact with portions of bases and/or polynucleotide backbone structures accessible in both forms of DNA (29,30). Some also react with phospholipids, which have no purine or pyrimidine base (4,5).…”

Section: Discussionmentioning

confidence: 99%

Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.

Zouali¹,

Stollar²

1986

J. Clin. Invest.

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To further our understanding of the molecular basis of DNAautoantibody interactions, we have characterized the specificities of three IgG human myeloma proteins that bind DNA. We measured their binding to synthetic single-and double-stranded homopolynucleotides, random and alternating copolymers, oligonucleotides, and nucleotides or nucleosides conjugated to nonnucleic acid carriers. All three antibodies bound single-stranded nucleic acids, including both polyribonucleotides and polydeoxyribonucleotides. They varied in relative affinities for polynucleotides of varying base composition. Polymers containing the purines guanine or hypoxanthine and/or the pyrimidine thymine were most reactive with all three proteins. A myeloma protein that reacted with poly(G), poly(I), or poly(dT) also bound to the corresponding nucleosides or nucleotides conjugated to bovine serum albumin. None of the antibodies reacted with base-paired double-helical polynucleotides (double-stranded RNA, RNA-DNA hybrid or double-stranded DNA). The results indicate that base specificity is prominent in their reactions and that the accessible epitopes in single-stranded polynucleotides become masked upon base pairing in double-stranded helices. These findings suggest a model in which positions N1 and 06 of guanine and hypoxanthine and N3 and 04 of thymine interact with amino acids of the antibody-combining site.

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Section: Discussionmentioning

confidence: 99%

Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.

Zouali¹,

Stollar²

1986

J. Clin. Invest.

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“…Some lupus autoantibodies react with denatured but not native DNA, whereas others react with both forms-usually better with the denatured DNA. Less common are antibodies with a true selectivity for the native form (9,11). As native DNA has not been an effective immunogen in experimental animals, the autoimmune subjects are the primary sources of antibodies that react with it.…”

mentioning

confidence: 99%

A recognition site on synthetic helical oligonucleotides for monoclonal anti-native DNA autoantibody.

Stollar¹,

Zon²,

Pastor³

1986

Proc. Natl. Acad. Sci. U.S.A.

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The binding site in native DNA for a murine monoclonal anti-DNA autoantibody was investigated by measurements of competitive binding of a series of synthetic helical oligonucleotides. The antibody bound to a (dG-dC)3 or (dGdC)4 core in the center of a base-paired octadecanucleotide. Reactions of analogues containing modifications or substitutions at specific sites indicated that the antibody bound to portions of cytosine and guanine in the major groove, a limited region of the backbone, and the 2-amino group of one guanine in the minor groove. For these interactions to occur, the antibody combining site would straddle the backbone of one of the helical strands of DNA.

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“…The high affinity anti-dsDNA antibodies did not bind significantly to ssDNA, which is unusual. Stollar & Papalian [28] have shown that ssDNA. prepared in a similar though not identical manner to the ssDNA we used, does maintain some secondary, native DNA-Iike structure.…”

Section: Discussionmentioning

confidence: 98%

Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients

Ehrenstein¹,

Longhurst²,

Isenberg³

1993

Clinical and Experimental Immunology

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SUMMARYThis study compares recently devised tnethods for producing IgG anti-DNA MoAbs from patients with SLE and analyses the antibodies generated from one patient at different phases of disease. Lymphocytes from SLE patients were transformed with Epstein-Barr virus (EBV) and/or fused with a heteromyeloma cell line., CB-F7. Direct fusion with CB-F7 resulted in the highest proportion of lgG-secreting lines, whereas EBV transformation resulted in a high percentage of IgM-secreting lines. Using direet fusion, five IgM anti-DNA antibody-seereting hybridomas were generated using lymphoeytes from a patient with relatively inactive SLE. Six months later when the disease was active, only IgG anti-DNA antibodies were produced. The antigen-binding patterns of the MoAbs were analysed. Only one of the IgM anti-DNA antibodies reacted with dsDNA by ELISA and none by Crithidia immunofluorescenee, whereas two ofthe IgG antibodies reacted with dsDNA by ELISA and Crithidia but did not bind to ssDNA. Only the two IgG high affinity anti-dsDNA antibodies bound to histones, and this was enhanced by added DNA. whereas three IgM antibodies bound lo cardiolipin. This study supports the notion that MoAbs derived from a patient with SLE represent those found in the serum of SLE patients at different stages of disease aetivity. The binding to histones by the two IgG anti-dsDNA antibodies supports the recently expressed view that antibodies binding DNA/histone may be important in the pathogenesis of SLE.

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Secondary Structure in Denatured DNA is Responsible for Its Reaction with Antinative DNA Antibodies of Systemic Lupus Erythematosus Sera

Cited by 61 publications

References 33 publications

Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.

Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.

A recognition site on synthetic helical oligonucleotides for monoclonal anti-native DNA autoantibody.

Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients

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