Monoclonal Anti-DNA antibodies

Structure, specificity, and biology

Tony Marion, Meera R. Krishnan, Dharmesh D. Desai, Nainn Tsyr Jou, David M. Tillman

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Anti-DNA antibodies are a major contributor to the pathogenesis associated with the autoimmune disease systemic lupus erythematosus in mice and human. The accumulation of a large body of structural information on autoimmune anti-DNA antibodies over the past several years, particularly from mice, has provided considerable insight into the structure, function, and biology of this important class of autoantibodies. Even though the germline repertoire of light and heavy chain variable regions that may encode DNA-specific antibodies is very large in mice, there are individual light and heavy chain variable region genes that have been recurrent and preferentially expressed among anti-DNA hybridomas. This has been particularly true for hybridomas producing antibodies that bind duplex, B-form, mammalian DNA (dsDNA). Recurrent somatically derived variable region structures, particularly arginines in the third complementary-determining region of the heavy chain (VH-CDR3), have also been recurrent and preferentially expressed among monoclonal anti-DNA antibodies. In fact specificity for dsDNA can be correlated to the relative amino acid position at which arginines are expressed within VH-CDR3 of anti-DNA. Most important from the results of structural analyses of monoclonal anti-DNA autoantibodies has been the realization that autoimmunity to DNA results from a clonally selective, antigen-specific immune response to DNA. Autoimmune antibodies to DNA have all of the characteristics of secondary immune antibodies. In further support of this hypothesis, we have been able to induce anti-DNA antibodies in normal, nonautoimmune mice by immunization with immunogenic DNA-peptide complexes. The induced antibodies have all of the structural and functional characteristics of autoimmune anti-DNA including the pathogenetic potential to induce glomerulonephritis. This review summarizes the results of research from our laboratory that support the above conclusions.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalMethods: A Companion to Methods in Enzymology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1997

Fingerprint

Antibody Specificity
Anti-Idiotypic Antibodies
Monoclonal Antibodies
Antibodies
Hybridomas
Autoantibodies
Arginine
Light
Histocompatibility Antigens Class II
Glomerulonephritis
Autoimmunity
Systemic Lupus Erythematosus
Autoimmune Diseases
Immunization
Amino Acids
Peptides
Research
Genes
Antigens

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Monoclonal Anti-DNA antibodies : Structure, specificity, and biology. / Marion, Tony; Krishnan, Meera R.; Desai, Dharmesh D.; Jou, Nainn Tsyr; Tillman, David M.

In: Methods: A Companion to Methods in Enzymology, Vol. 11, No. 1, 01.01.1997, p. 3-11.

Research output: Contribution to journalArticle

Marion, Tony ; Krishnan, Meera R. ; Desai, Dharmesh D. ; Jou, Nainn Tsyr ; Tillman, David M. / Monoclonal Anti-DNA antibodies : Structure, specificity, and biology. In: Methods: A Companion to Methods in Enzymology. 1997 ; Vol. 11, No. 1. pp. 3-11.
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