Epitopes described in "Retargeting T cell-mediated inflammation: a new perspective on autoantibody action."

Article Authors:Y H Lou; K K Park; S Agersborg; P Alard; K S Tung
Article Title:Retargeting T cell-mediated inflammation: a new perspective on autoantibody action.
Reference Detail
Reference ID:1017041
Abstract:To understand the pathogenesis of organ-specific autoimmune disease requires an appreciation of how the T cell-mediated inflammation is targeted, and how the organ function is compromised. In this study, autoantibody was documented to influence both of these parameters by modulating the distribution of T cell-mediated inflammation. The murine autoimmune ovarian disease is induced by immunization with the ZP3330-342 peptide of the ovarian zona pellucida 3 glycoprotein, ZP3. Passively transferred or actively induced Ab to ZP3335-342 bound to the zona pellucida in the functional and degenerative ovarian follicles, and the ovaries remained histologically normal. Transfer of ZP3330-342 peptide-specific T cells targeted the degenerative follicles and spared the functional follicles, and the resultant interstitial oophoritis was associated with unimpaired ovarian function. Unexpectedly, the coexistence of ZP3330-342 peptide-specific T cells and zona-bound autoantibody led to a dramatic translocation of the ovarian inflammation to the growing and mature ovarian follicles, with destruction of the ovarian functional unit. Ab retargeted both Th1-induced mononuclear inflammation and Th2-induced eosinophilic inflammation, and retargeting was induced by murine and rat polyclonal Abs to multiple distinct native B cell determinants of the zona pellucida. Therefore, by reacting with the native determinants in tissue Ag, Ab alters the distribution of T cell-mediated inflammation, and results in destruction of the functional units of the target organ. We propose that this is a clinically important and previously unappreciated element of Ab action in autoimmune disease.
Affiliations:Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. ylou@mail.db.uth.tmc.edu
Reference Type:Literature
PubMed ID:10799886
Journal:J Immunol
Journal Volume:164
Article Pages:5251-7
Journal ISSN:0022-1767
Article Chemical List:Autoantibodies;Cytokines;Egg Proteins;Epitopes, T-Lymphocyte;Membrane Glycoproteins;Receptors, Cell Surface;zona pellucida glycoproteins
Article MeSH List:Amino Acid Sequence; Animals; Antibody Specificity; Atrophy; Autoantibodies(administration & dosage; physiology); Autoimmune Diseases(etiology; immunology; pathology); Cytokines(physiology); Egg Proteins(administration & dosage; immunology); Epitopes, T-Lymphocyte(immunology); Female; Humans; Injections, Subcutaneous; Lymphocyte Transfusion; Membrane Glycoproteins(administration & dosage; immunology); Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; Oophoritis(etiology; immunology; pathology); Organ Specificity(immunology); Ovarian Follicle(immunology; pathology); Receptors, Cell Surface; T-Lymphocytes(immunology; pathology; transplantation); Zona Pellucida(immunology; pathology)
Curation Last Updated:2015-07-30 20:33:35