title: Association of New Putative Epitopes of Myelin Proteolipid Protein (58-74) with Pathogenesis of Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity. PLP58-74 was considered as an immunodominant epitope candidate of PLP using bioinformatics tools. Patients and healthy individuals' peripheral blood mononuclear cells (PBMCs) were treated with PLP58-74 and its proliferative effects were evaluated through assessing proliferating cell nuclear antigen (PCNA) gene expression changes by real time PCR and immunocytochemistry assay. Finally, the rate of CD4+ and CD8+ T cells were assessed by flowcytometry. ELISA was also performed to measure anti PLP58-74 antibody in patients' serum. PLP58-74 induced proliferation in patients' PBMCs while it did not influence PBMCs of healthy individuals. CD4+ T cells were the main activated cells in reaction to PLP58-74 which increased from 22% to 39.91%. In addition, immune assay showed threefold increase in specific anti PLP58-74 IgG in patients compared to healthy controls. Results showed that PLP58-74 can stimulate CD4+ T cells and humoral immunity. Therefore it seems that the epitopes of some microorganisms mimicking PLP such as PLP58-74 might have a potential role in the initiation of MS.
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Zamanzadeh
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ahangari
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Ataei
authors.affiliation: Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Samie
authors.initials: S
authors.lastname: Pouragahi
authors.affiliation: Department of Neurology , Shahed University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Massood
authors.initials: SM
authors.lastname: Nabavi
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: Department of Medical Genetic, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sanati
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D018991:Myelin Proteolipid Protein; D018809:Proliferating Cell Nuclear Antigen
keywords: Autoimmune disease; Experimental autoimmune encephalomyelitis; Molecular mimicry; Multiple sclerosis; Myelin proteolipid protein