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In silico Epitope Mapping of Glucose-6-Phosphate Isomerase: A Rheumatoid Arthritis Autoantigen

  • Rheumatoid arthritis-like symptoms can be initiated experimentally in naive K/BxN mice by simultaneously administering the two monoclonal antibodies 11H3 and 46H9. Both antibodies specifically recognize Glucose-6-Phosphate Isomerase (GPI), a known auto antigen in RA patients. Amino acid sequences of the Fv parts of the antibodies were determined by translating the respective hybridoma DNA sequences and served for threedimensional structure modeling of the paratope regions. In silico docking of both Fv antibody structure models to the X-ray structures of the homodimeric murine GPI as well as to the homodimeric human GPI predicted the murine epitope of the 11H3 antibodies to comprise partial amino acid sequences QRVRSGDWKGYTGKS (aa134-148) and AAKDPSAVAK (aa232-241), generating an assembled (conformational) epitope. The 11H3 epitope on human GPI encompasses the matching partial amino acid sequences QRVRSGDWKGYTGKT (aa134-148) and AAKDPSAVAK (aa232-241). The epitope of the 46H9 antibody was determined to consist of the partial murine GPI amino acid sequence RKELQAAGKSPEDLEK (aa446-461) and the human GPI amino acid sequence RKELQAAGKSPEDLER (aa446-461), respectively, resembling consecutive (linear) epitopes. The predicted epitopes were verified by mass spectrometric epitope mapping using synthetic epitope peptides. Peptide QRVRSGDWKGYTGKS[GSMSGS] AAKDPSAAK included a small spacer sequence in between the epitope sequences, mimicking the assembled epitope for the 11H3 antibody. The peptide RKELQAAGKSPEDLEK represented the consecutive epitope for the 46H9 antibody. The determined B-cell epitopes of GPI and their interactions with the monoclonal antibodies provide a detailed structural understanding of immunological disease onset mechanisms in a mouse model of rheumatoid arthritis.

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Document Type:Article
Author:KFM Opuni, S Solomon, F Metzen, D Frommholz, C Koy, C Röwer, MO Glocker, H Illges, PC Anderson
Parent Title (English):Journal of Proteomics & Bioinformatics
First Page:60
Last Page:72
Publisher:OMICS International
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2017/03/15
Copyright:© 2017 Opuni KFM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Keyword:Docking; Epitope mapping: Epitope extraction; In silico epitope prediction; Mass spectrometry; Molecular dynamics
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2018/06/06
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 3.0