title: p185, an immunodominant epitope, is an autoantigen mimotope.
abstract: An immunodominant peptide (p185(378-394)) derived from the c-erbB2 gene product, was recognized by an anti-DNA antibody, B3, and importantly by two classical DNA-binding proteins, Tgo polymerase and Pa-UDG. These reactivities were inhibited by DNA, confirming that the peptide mimicked DNA. BALB/c mice immunized with p185(378-394) developed significant titers of IgG anti-dsDNA antibodies. Screening of 39 human lupus sera revealed that 5% of these sera possessed reactivity toward p185(378-394). Representative mouse and human sera with anti-p185(378-394) reactivity bound intact p185, and this binding was inhibited by dsDNA. This is the first demonstration of a naturally occurring autoantigen mimotope. The present study identifies a potential antigenic stimulus that might trigger systemic lupus erythematosus in a subset of patients.
authors.affiliation: Centre for Rheumatology, University College London Division of Medicine, University College London Hospital, London W1T 4JF, UK. s.kumar@ucl.ac.uk
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: John A
authors.initials: JA
authors.lastname: Hinks
authors.forename: Joseph
authors.initials: J
authors.lastname: Maman
authors.forename: Chelliah T
authors.initials: CT
authors.lastname: Ravirajan
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Pearl
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D004247:DNA; D004268:DNA-Binding Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases