Epitopes described in "Identification of an epitope within human integrin alpha 6 subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid."

Article Authors:Khwaja Aftab Rashid; Joel N H Stern; A Razzaque Ahmed
Article Title:Identification of an epitope within human integrin alpha 6 subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid.
Reference Detail
Reference ID:1017271
Abstract:Oral pemphigoid (OP) is a rare chronic autoimmune disease characterized by blisters and erosive lesions in the oral mucosa. We identified an epitope for the binding of OP autoantibodies within the integrin alpha6 subunit, by cloning four overlapping fragments (A, B, C, and D). Immunoperoxidase studies demonstrated that all of the fragments were present in the oral mucosa. Sera of 20 patients with active OP were studied. All sera bound to integrin alpha6 in DU145 cell lysate by immunoprecipitation and immunoblot assay. The same sera bound only to fragment A and its subfragment A2 on an immunoblot assay. The specificity of the binding was further characterized by blocking and cross-absorption studies. A 14-aa synthetic peptide A2.1, within fragment A2, bound to all the test sera. The sera in this study bound to only one epitope. Controls were sera samples from 10 healthy volunteers and 40 patients with other variants of mucous membrane pemphigoid and mAb GoH3 and BQ16 to integrin alpha6. Control sera did not bind to the full-length integrin alpha6 subunit nor any of the cloned fragments. The OP patient sera and immunoaffinity-purified OP sera, rabbit antisera against fragments A and A2, and mAb GoH3 produced basement membrane separation of oral mucosa in organ culture. This study identifies a peptide within the extracellular domain of integrin alpha6 molecule, to which Abs in the sera from patients with OP bind, and which may play an important role in the pathogenesis of OP.
Affiliations:Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Reference Type:Literature
PubMed ID:16424229
Journal:J Immunol
Journal Volume:176
Article Pages:1968-77
Journal ISSN:0022-1767
Article Chemical List:Autoantibodies;Epitopes;Immunoglobulin Fragments;Integrin alpha6;Protein Subunits
Article MeSH List:Autoantibodies(metabolism; physiology); Basement Membrane(immunology; pathology); Binding Sites, Antibody; Epitopes(immunology; metabolism); Extracellular Space(immunology; metabolism); Humans; Immunoenzyme Techniques; Immunoglobulin Fragments(immunology); Integrin alpha6(immunology; metabolism); Microscopy, Confocal; Mouth Diseases(immunology; pathology); Mouth Mucosa(immunology; pathology); Organ Culture Techniques; Pemphigoid, Bullous(immunology; metabolism; pathology); Protein Subunits(immunology; metabolism)
Curation Last Updated:2015-07-24 20:09:37