The Interaction of Anti-DNA Antibodies with DNA: Evidence for Unconventional Binding Mechanisms |
| |
Authors: | David S. Pisetsky Angel Garza Reyna Morgan E. Belina Diane M. Spencer |
| |
Affiliation: | 1.Department of Medicine and Immunology, Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC 27710, USA;2.Medical Research Service, Veterans Administration Medical Center, Durham, NC 27705, USA;3.Epigenomic Regulation in Development and Cancer Team, Broad Institute of MIT and Harvard, Boston, MA 02142, USA;4.Duke University School of Medicine, Duke University, Durham, NC 27705, USA; |
| |
Abstract: | 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. |
| |
Keywords: | DNA anti-DNA antibodies systemic lupus erythematosus avidity monogamous bivalency |
|
|