title: Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice.
abstract: We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139-151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89-101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108-120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89-101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108-120 develop encephalomyelitis similar to the disease induced by the cognate peptide. We demonstrate that NAD 108-120 induces T cells that cross-react with MBP 89-101; the antigen-sensitized T cells, which produce predominantly T helper (T(h)) 1 and T(h)17 cytokines, transfer disease in naive SJL recipients reminiscent of the disease induced with MBP 89-101. This is the first report to demonstrate that a solitary microbe can induce CNS autoimmunity by generating cross-reactive T cells for multiple myelin antigens.
authors: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
authors: Chandirasegaran
authors: C
authors: Massilamany
authors: Oluwatoyin A
authors: OA
authors: Asojo
authors: Arunakumar
authors: A
authors: Gangaplara
authors: David
authors: D
authors: Steffen
authors: Jay
authors: J
authors: Reddy
mesh_terms: D048248:Acanthamoeba castellanii / Q000276:immunology*; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C446766:myelin basic protein 89-101; D009245:NADH Dehydrogenase