title: MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8⁺ T cells.
abstract: Myelin presentation to T cells in the central nervous system (CNS) sustains inflammation in multiple sclerosis (MS). CD4(+) and CD8(+) T cells contribute to MS, but only cells that present myelin to CD4(+) T cells have been identified. We show that MHC class I-restricted myelin basic protein (MBP) was presented by oligodendrocytes and cross-presented by Tip-dendritic cells (DCs) during experimental autoimmune encephalomyelitis (EAE), an animal model of MS initiated by CD4(+) T cells. Tip-DCs activated naive and effector CD8(+) T cells ex vivo, and naive MBP-specific CD8(+) T cells were activated in the CNS during CD4(+) T cell-induced EAE. These results demonstrate that CD4(+) T cell-mediated CNS autoimmunity leads to determinant spreading to myelin-specific CD8(+) T cells that can directly recognize oligodendrocytes.
authors.affiliation: Department of Immunology, University of Washington, Seattle, Washington, USA.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ji
authors.forename: Luca
authors.initials: L
authors.lastname: Castelli
authors.forename: Joan M
authors.initials: JM
authors.lastname: Goverman
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002490:Central Nervous System / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D000939:Epitopes; D004676:Myelin Basic Protein