title: A charged segment mainly composed of basic amino acids forms an autoepitope of CENP-A.
abstract: Autoantibodies against centromere proteins are commonly found in the serum of patients with scleroderma and other systemic autoimmune diseases. The reactivity of anticentromere autoantibodies (ACA) from 78 patients was investigated by ELISA using two kinds of a 15-amino-acid peptide corresponding to the N- and C-termini of CENP-A, one of the target molecules of ACA. The N-terminal peptide (residues 3-17) was recognized by 85% of ACA, while the C- terminal peptide (residues 126-140) was not. The ELISA result for the N-terminal peptide correlated with the immunoreactivity of CENP-A observed in immunoblotting. Moreover, the binding between autoantibodies and CENP-A was inhibited by the N-terminal peptide in 98.5% of anti-CENP-A- positive sera in immunoblotting. The sequence of peptide, PRRRSRKPEAPRRRS, is highly charged and has two repeats of PRRRS. These results indicate that the N-terminal-charged region forms a major epitope of CENP-A. This area may be involved in the induction of specific autoantibodies against centromere in autoimmune patients.
authors.affiliation: Department of Dermatology, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Muro
authors.forename: T
authors.initials: T
authors.lastname: Iwai
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
mesh_terms: D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000737:chemistry; D000937:Antigen-Antibody Reactions; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology; D002503:Centromere / Q000276:immunology; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D016056:Immunodominant Epitopes