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Fine mapping of a monoclonal antibody to the N ‐Methyl D ‐aspartate receptor reveals a short linear epitope
Author(s) -
Amrutkar Surekha Dipak,
Trier Nicole Hartwig,
Hansen Paul Robert,
Houen Gunnar
Publication year - 2012
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22165
Subject(s) - epitope , chemistry , antigenicity , amino acid , epitope mapping , monoclonal antibody , linear epitope , biochemistry , extracellular , peptide , antibody , peptide sequence , receptor , microbiology and biotechnology , nmda receptor , biology , immunology , gene
Abstract Anti‐N‐Methyl D ‐aspartate receptor encephalitis is an autoimmune disease in which autoantibodies are produced against extracellular regions of the N‐Methyl D ‐aspartate receptor (NMDAR). In this study, we used resin‐bound peptides equipped with a base labile linker to map the epitope of a monoclonal NMDAR antibody against the NMDAR NR1 subunit. The antigenicity of the synthesized resin‐bound peptides was determined by enzyme‐linked immunosorbent assay. Distinct reactivity was found to two extracellular overlapping peptides (amino acids, 658–687). Using N‐ and C‐terminally truncated resin‐bound peptides, the minimum functional epitope was identified as the NPSDK sequence. The peptide sequence RNPSDK (amino acids, 673–678) was identified as the complete epitope, which was found to be located in the extracellular S2 domain of the NR1 subunit. Especially, the N‐terminal arginine residue was found to be essential for reactivity, whereas the remaining amino acids could be replaced with amino acids of similar side‐chain functionality, indicating the importance of backbone interaction in antibody reactivity. © 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 567–575, 2012.