My projects currently focus on the pathways and cell interactions in CD8-mediated and antibody-associated brain diseases. In CD8-mediated brain diseases, cytotoxic T cells (CTLs) infiltrate the CNS and can target different cell types which leads to a variety of clinical diseases, depending on which cells and which regions of the CNS are targeted. Besides Multiple Sclerosis, CD8-mediated responses can be found in a variety of neuroinflammatory conditions. Roughly, these CD8-mediated encephalitides can be divided into three groups; The first are viral encephalitides, in which a cytotoxic T cell mediated response is directed against infected cells. Second, the classical autoimmune paraneoplastic encephalitides with antibodies, against intracellular or intranuclear (i.e anti-hu, anti-Ma2 and anti-Yo) antigens. Here, cytotoxic T lymphocytes (CTLs), primed by a peripheral neoplasm, attack CNS neurons expressing the same antigens (i.c. oncogenes) that are found in the peripheral tumor. Besides these viral and paraneoplastic encephalitis groups, a third group consists of encephalitides with an unknown etiology but a distinct cytotoxic T cell response against CNS neurons. At present we are working on three CD8-mediated diseases: Susac syndrome (Gross et al., Nat Comm 2029), Narcolepsy type I and Rasmussen Encephalitis.