title: The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets.
abstract: Identification of the target antigens of pathogenic antibodies and T cells is of fundamental importance for understanding the pathogenesis of multiple sclerosis, and for the development of personalised treatments for the disease. Myelin-specific CD4+ T cells emerged long ago as a key player in animal models of multiple sclerosis. Taking a forward-translational approach, autoreactive CD4+ T cells have been studied extensively in patients with multiple sclerosis, and there is evidence, but as yet no direct proof, that autoreactive CD4+ T cells are a key player in the pathogenesis of the disorder. Several therapies that selectively target myelin-specific CD4+ T cells have been investigated in clinical trials up to phase 3. So far, however, none of these (mostly underpowered) therapeutic trials have provided definitive evidence of clinical efficacy. One major obstacle to personalised, highly selective immunotherapy is the absence of standardised and reliable assays to assess antigen-specific human T-cell responses. Such assays would be essential for stratification of patients with multiple sclerosis according to their individual target antigens.
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: D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000592:standards*; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy
chemical_list: D000941:Antigens; D001323:Autoantibodies