MIMOTOPES OF POLYREACTIVE ANTI-DNA ANTIBODIES IDENTIFIED USING PHAGE-DISPLAY PEPTIDE LIBRARIES

Citation
P. Sibille et al., MIMOTOPES OF POLYREACTIVE ANTI-DNA ANTIBODIES IDENTIFIED USING PHAGE-DISPLAY PEPTIDE LIBRARIES, European Journal of Immunology, 27(5), 1997, pp. 1221-1228
Citations number
22
Categorie Soggetti
Immunology
ISSN journal
00142980
Volume
27
Issue
5
Year of publication
1997
Pages
1221 - 1228
Database
ISI
SICI code
0014-2980(1997)27:5<1221:MOPAAI>2.0.ZU;2-6
Abstract
Three monoclonal IgG2a anti-DNA polyreactive autoantibodies, derived f rom lupus-prone mice (NZB x NZW)F1, were studied by surface plasmon re sonance (BIAcore) analysis using three different synthetic double-stra nded (ds) oligonucleotides of 25, 30, and 25 base pairs (bp). These mo noclonal antibodies (mAb) exhibited dissociation rate constants (k(off )) ranging from 0.0001 (mAb F14.6 and F4.1) to 0.01/s (mAb 520.8) and k(on) ranging from 2 x 10(5) to 2 x 10(6) /M/s. The screening of a con strained random peptide library displayed on M13 bacteriophages on the se mAb allowed the determination of the specific consensus motifs (mim otopes) for mAb F14.6 and 520.8, but not for mAb F4.1. No cross-reacti on was observed between F14.6- and J20.8-specific peptides (and vice v ersa). Binding of all phages selected on F14.6 was inhibited with 700 ng/ml soluble DNA. The binding of one group of peptides selected on 52 0.8 was inhibited by 400 ng/ml soluble DNA, of a second group by 2500 ng/ml, while binding of a third group could not be inhibited. The dete rmined consensus sequences do not match with known sequences. Peptides specific for F14.6 share negative charges and aromatic rings that may mimic a DNA backbone, while peptides selected with 520.8 do not bear any negative charge, implying a different kind of molecular recognitio n, for example hydrogen or salt bonds. The peptides selected on 520.8 also bind serum antibodies from human patients with systemic lupus ery thematosus. In addition, BALB/c mice immunized with some of the select ed phages exhibit high serum titers of IgG3 anti-dsDNA antibodies, fur ther supporting the hypothesis that peptide epitopes may mimic an olig onucleotide structure.