TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Opuni, KFM
A1  - Solomon, S
A1  - Metzen, F
A1  - Frommholz, D
A1  - Koy, C
A1  - Röwer, C
A1  - Glocker, MO
A1  - Illges, H
A1  - Anderson, PC
T1  - In silico Epitope Mapping of Glucose-6-Phosphate Isomerase: A Rheumatoid Arthritis Autoantigen
JF  - Journal of Proteomics & Bioinformatics
N2  - 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.
KW  - In silico epitope prediction
KW  - Epitope mapping: Epitope extraction
KW  - Molecular dynamics
KW  - Docking
KW  - Mass spectrometry
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-36800
SN  - 0974-276X
SS  - 0974-276X
U6  - https://doi.org/10.4172/jpb.1000425
DO  - https://doi.org/10.4172/jpb.1000425
VL  - 10
IS  - 3
SP  - 60
EP  - 72
PB  - OMICS International
ER  -