title: The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research.
abstract: Interest in CD8+ T cells and B cells was initially inspired by observations in multiple sclerosis rather than in animal models: CD8+ T cells predominate in multiple sclerosis lesions, oligoclonal immunoglobulin bands in CSF have long been recognised as diagnostic and prognostic markers, and anti-B-cell therapies showed considerable efficacy in multiple sclerosis. Taking a reverse-translational approach, findings from human T-cell receptor (TCR) and B-cell receptor (BCR) repertoire studies provided strong evidence for antigen-driven clonal expansion in the brain and CSF. New methods allow the reconstruction of human TCRs and antibodies from tissue-infiltrating immune cells, which can be used for the unbiased screening of antigen libraries. Myelin oligodendrocyte glycoprotein (MOG) has received renewed attention as an antibody target in childhood multiple sclerosis and in a small subgroup of adult patients with multiple sclerosis. Furthermore, there is growing evidence that a separate condition in adults exists, tentatively called MOG-antibody-associated encephalomyelitis, which has clinical features that overlap with neuromyelitis optica spectrum disorder and multiple sclerosis. Although CD8+ T cells and B cells are thought to have a pathogenic role in some subgroups of patients, their target antigens have yet to be identified.
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Campus Martinsried-Grosshadern, Ludwig-Maximilians University, Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany. Electronic address: reinhard.hohlfeld@med.uni-muenchen.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Campus Martinsried-Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Campus Martinsried-Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
authors.affiliation: HERTIE Senior Professor Group Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D057170:Translational Research, Biomedical
chemical_list: D001323:Autoantibodies; D001324:Autoantigens