Epitope mapping of human aromatic L-amino acid decarboxylase.
Autoimmune polyendocrine syndrome type I (APS I) is a rare hereditary condition considered a model disease for organ specific autoimmunity. A wide range of autoantibodies targeting antigens present in the affected organs have been identified. Autoantibodies against aromatic L-amino acid decarboxylase (AADC) are present in about 50% of APS I patients. In order to increase our understanding of autoantibody specificity in APS I, the aim of the present study was to localize target regions on AADC recognized by sera from APS I patients. Using several complementing strategies, we have shown that autoantibodies against AADC mainly recognize conformational epitopes. The major antigenic determinants were detected N-terminally to amino acid residue 237. Replacement of amino acids 227-230 (ERDK) with alanine residues reduced the reactivity towards AADC by >80% in all patient sera tested, suggesting that amino acids 227-230 are an important part of an immunodominant epitope.
Bratland
Eirik
E
Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway. eirik.bratland@student.uib.no
Wolff
Anette S Bøe
AS
Haavik
Jan
J
Kämpe
Olle
O
Sköldberg
Filip
F
Perheentupa
Jaakko
J
Bredholt
Geir
G
Knappskog
Per M
PM
Husebye
Eystein S
ES
D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies; D002262:Carboxy-Lyases / Q000235:genetics / Q000276:immunology; D018604:Epitope Mapping / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology
D001323:Autoantibodies; D011993:Recombinant Fusion Proteins; D002262:Carboxy-Lyases; D001142:Aromatic-L-Amino-Acid Decarboxylases; C019972:sulfoalanine decarboxylase