title: Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis.
abstract: Qa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8+regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients. Hence, we asked whether the CD8+Treg cells could directly target the myelin sheath to ameliorate EAE. To address this question, we analyzed Qa-1 epitopes in myelin oligodendrocyte glycoprotein (MOG that is a protein in myelin sheath). Here, we report identification of a MOG-specific Qa-1 epitope. Immunization with this epitope suppressed ongoing EAE, which was abrogated by CD8+T cell depletion. Additionally, the epitope immunization activated the epitope-specific CD8+T cells which specifically accumulated in the CNS-draining cervical lymph nodes. Finally, CD8+T cells primed by the epitope immunization transferred EAE suppression. Hence, this study reveals a novel regulatory mechanism mediated by the CD8+Treg cells. We propose that immunization with myelin-specific HLA-E epitopes (human homologues of Qa-1 epitopes) is a promising therapy for MS.
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.|Division of Infectious Disease, Jinan Infectious Disease Hospital, Shandong University, 22029 Jing-Shi Road, Jinan, 250021, P.R. China.
authors: Xiaohua
authors: X
authors: Wang
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.|Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
authors: Jintao
authors: J
authors: Zhang
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.
authors: David J
authors: DJ
authors: Baylink
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.|Department of Emergency Medicine, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Graduate Institute of Clinical Medical Sciences, School of Medicine, Chang-Gung university, Taoyuan, Taiwan.
authors: Chih-Huang
authors: CH
authors: Li
authors: Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
authors: Douglas M
authors: DM
authors: Watts
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.
authors: Yi
authors: Y
authors: Xu
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.|Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California, USA.
authors: Xuezhong
authors: X
authors: Qin
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.
authors: Michael H
authors: MH
authors: Walter
authors: Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.
authors: Xiaolei
authors: X
authors: Tang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D063308:Myelin-Oligodendrocyte Glycoprotein; C032907:Q surface antigens