DNA mimics a self-protein that may be a target for some anti-DNA antibodies in systemic lupus erythematosus
Zack, D.J.; Yamamoto, K.; Wong, A.L.; Stempniak, M.; French, C.; Weisbart, R.H.
Journal of Immunology 154(4): 1987-1994
1995
ISSN/ISBN: 0022-1767 PMID: 7836777 Document Number: 446171
Recent studies suggest that some anti-DNA Abs in systemic lupus erythematosus may actually be Abs to specific proteins and that binding to dsDNA is a nonspecific cross-reactive event. To identify such proteins that bind to anti-DNA Abs, a cDNA expression library from human placenta was screened with mAb 3E10, a pathogenic anti-dsDNA Ab. MAb 3E10 was shown to bind to a 44-amino-acid fragment of HP8, a newly identified protein with amino acid sequence homology to the family of SPARC extracellular matrix proteins. To determine if Ab binding to both dsDNA and HP8 protein occurs through a common binding site, and therefore represents molecular mimicry, the Ab binding domains for protein and DNA were mapped. Chain recombinations between mAb 3E10 and a non-anti-DNA mAb showed that both the heavy and the light chains of mAb 3E10 were essential for anti-dsDNA and anti-HP8 reactivity. Mutagenesis experiments demonstrated that dsDNA and HP8 shared several critical binding residues located in all three complementarity-determining regions of mAb 3E10 V-H. Moreover, Abs to HP8 were demonstrated in the sera of a subset of lupus patients. These results indicate that DNA mimics the HP8 protein in binding a lupus Ab, and that this protein may be a target for a subpopulation of anti-dsDNA Abs in systemic lupus erythematosus.