The Interaction of Anti-DNA Antibodies with DNA: Evidence for Unconventional Binding Mechanisms.

Journal Article (Review;Journal Article)

Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus, a prototypic autoimmune disease. These antibodies bind to conserved sites on single-stranded and double-stranded DNA and display variable region somatic mutations consistent with antigen selection. Nevertheless, the interaction of anti-DNA with DNA has unconventional features. Anti-DNA antibodies bind by a mechanism called monogamous bivalency, in which stable interaction requires contact of both Fab sites with determinants on the same extended DNA molecule; the size of this DNA can be hundreds to thousands of bases, especially in solid phase assays. This binding also requires the presence of the Fc portion of IgG, a binding mechanism known as Fc-dependent monogamous bivalency. As shown by the effects of ionic strength in association and dissociation assays, anti-DNA binding is primarily electrostatic. Like anti-DNA autoantibodies, anti-DNA antibodies that bind specifically to non-conserved sites on bacterial DNA, a type of anti-DNA found in otherwise healthy individuals, also interact by monogamous bivalency. The unconventional features of anti-DNA antibodies may reflect the highly charged and polymeric nature of DNA and the need for molecular rearrangements to facilitate monogamous bivalency; the Fc portion contributes to binding in an as yet unknown way.

Full Text

Duke Authors

Cited Authors

  • Pisetsky, DS; Garza Reyna, A; Belina, ME; Spencer, DM

Published Date

  • May 7, 2022

Published In

Volume / Issue

  • 23 / 9

Start / End Page

  • 5227 -

PubMed ID

  • 35563617

Pubmed Central ID

  • PMC9105193

Electronic International Standard Serial Number (EISSN)

  • 1422-0067

International Standard Serial Number (ISSN)

  • 1422-0067

Digital Object Identifier (DOI)

  • 10.3390/ijms23095227

Language

  • eng