title: Mapping of linear epitopes of human histone H1 recognized by rabbit anti-H1/H5 antisera and antibodies from autoimmune patients.
abstract: Seventeen synthetic peptides of 15-16 residues, covering the complete sequence of the major human H1b variant, were tested for their capacity to bind serum IgG antibodies from 128 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (pSS). One peptide (residues 111-127) of the human H1 degree variant and six synthetic and natural fragments of H5 were also tested. Results were compared to those obtained with antibodies from 11 rabbits immunized against chicken H1 and H5, and calf H1. The activity of peptides was tested in direct ELISA and in inhibition assays with free peptides in solution. A major epitope recognized by antibodies from SLE, RA and pSS patients as well as by rabbit antibodies was identified in the C-terminus of H1b (residues 204-218). Other peptides in the globular (residues 79-94) and C-terminal domains of H1b and peptide 111-127 of H1 degree were also recognized, albeit at a lower level and frequency, and some of them contain sequence homologies with peptide 204-218. Patients' antibodies and rabbit antisera were tested with complete H1 proteins from HeLa cells, calf thymus and chicken erythrocytes and with chicken H5. Less than 25% of autoimmune sera contained IgG antibodies reacting with H1/H5 in a direct ELISA. In dot-immunoassay, antigenic activity with intact H1/H5 proteins was detected in a larger number of sera. Using antibodies raised in rabbits against peptides 1-16 and 204-218 of H1b, we found no reaction with H1 immobilized on a solid-phase. In contrast, peptides 144-159, 170-185 and 204-218, which contain identical structural domains, compete with H1 in solution indicating that any of these three regions are accessible at the surface of free H1 and may be involved in the induction of specific antibodies in autoimmune patients.
authors.affiliation: Laboratoire d'Immunochimie, UPR 9021 CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Stemmer
authors.forename: J P
authors.initials: JP
authors.lastname: Briand
authors.forename: S
authors.initials: S
authors.lastname: Muller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006657:Histones / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits; D012859:Sjogren's Syndrome / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006657:Histones; D007106:Immune Sera