Antigen processing and presentation in multiple sclerosis.
CD4(+) T cells play a central role in the pathogenesis of multiple sclerosis (MS). Generation, activation and effector function of these cells crucially depends on their interaction with MHC II-peptide complexes displayed by antigen presenting cells (APC). Processing and presentation of self antigens by different APC therefore influences the disease course at all stages. Selection by thymic APC leads to the generation of autoreactive T cells, which can be activated by peripheral APC. Reactivation by central nervous system APC leads to the initiation of the inflammatory response resulting in demyelination. In this review we will focus on how MHC class II antigenic epitopes are created by different APC from the thymus, the periphery and from the brain, and will discuss the relevance of the balance between creation and destruction of such epitopes in the context of MS. A solid understanding of these processes offers the possibility for designing future therapeutic strategies.
Stoeckle
Christina
C
Department of General Neurology, Hertie Institute for Clinical Brain Research, Otfried-Mueller-Str. 27, 72076, Tuebingen, Germany. christina.stoeckle@web.de
Tolosa
Eva
E
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001921:Brain / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C499048:MBP protein, human; C571326:MOG protein, human; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors