title: Fine mapping of a monoclonal antibody to the N-Methyl D-aspartate receptor reveals a short linear epitope.
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.
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen S 2300, Denmark.
authors.forename: Surekha Dipak
authors.initials: SD
authors.lastname: Amrutkar
authors.forename: Nicole Hartwig
authors.initials: NH
authors.lastname: Trier
authors.forename: Paul Robert
authors.initials: PR
authors.lastname: Hansen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018604:Epitope Mapping; D008969:Molecular Sequence Data; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016194:Receptors, N-Methyl-D-Aspartate