| Author/Editor | Žager, Urška; Kveder, Tanja; Čučnik, Saša; Božič, Borut; Lunder, Mojca | |
| Title | Anti-ß2-glycoprotein I paratopes and ß2-glycoprotein I epitopes characterization using random peptide libraries | |
| Type | članek | |
| Vol. and No. | Letnik 47, št. 7 | |
| Publication year | 2014 | |
| Volume | str. 438-444 | |
| ISSN | 0891-6934 - Autoimmunity | |
| Language | eng | |
| Abstract | Studies concerning interactions between anti-ß2-glycoprotein I antibodies (anti-ß2GPI) and ß2-glycoprotein I (ß2GPI) suggest relevance of charge interactions and hydrogen bonds. However, paratope of diagnostically and clinically relevant anti-ß2GPI and epitope characteristics of ß2GPI, still remain unclear. The aim of our study was to determine paratope characteristics of various anti-ß2GPI antibodies and epitope characteristics of ß2GPI using phage display. Monoclonal IgG anti-ß2GPI, purified polyclonal high avidity and low avidity IgG anti-ß2GPI derived from plasma of APS patients were used to screen phage display libraries. The affinity and competition ability of selected clones were evaluated. Various heptapeptides presenting putative paratopes of anti-ß2GPI and specific heptapeptides presenting putative epitopes of ß2GPI were determined. Epitope presenting peptides bind to the respective anti-ß2GPI and consequently interrupt antibody-antigen interaction. The amino acid composition of selected peptides confirmed the importance of hydrogen bonds and charge interactions in the binding of anti-ß2GPI to the antigen. Epitopes recognized by high avidity anti-ß2GPI predominately contain hydrogen bond forming side chains, while in low avidity anti-ß2GPI epitope the charged side chains prevail. The alignment of selected sequences to three-dimensional antigen structure revealed that polyclonal high avidity anti-ß2GPI recognize native epitopes that are accessible regardless of ß2GPI's conformation whereas the epitope recognized by low avidity anti-ß2GPI is cryptic and cannot be accessed when ß2GPI takes the closed plasma conformation. | |
| Descriptors | Antiphospholipid Syndrome Immunology | |
| Keywords | antibody-antigen interaction epitope mimetics paratope mimetics phage display |