Epstein-Barr virus induced T cell responses and the pathogenesis of multiple sclerosis. (360G-Wellcome-093580_Z_10_Z)

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) whose pathogenesis is widely accepted to be T cell-mediated, one possibility being that exposure to infectious agent(s) in certain individuals induces T cell responses that cross-react with epitopes derived from self-proteins expressed in the CNS. One prime candidate in this regard is Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a T cell-mediated immunopathologic disease which itself predisposes to MS. Recent reports suggest that T cell responses to one EBV antigen, EBNA1, differ in their fine specificity between MS patients and healthy controls, and include T cells that cross-recognise myelin-derived epitopes. Using our experience in EBV immunology, we plan to address these issues in more detail: (1) analysing the frequency, epitope range and autoreactive potential of EBV-specific CD4+ and CD8+ T cells in the blood of MS patients versus healthy controls with and without a history of IM, (2) determining the autoreactive potential of recently-identified CD4+ T cell responses against cellular antigens up-regulated in EBV-infected cells, (3) cloning T cells specific for central nervous system (CNS) protein epitopes from the cerebrospinal fluid (CSF) of selected MS patients and examining their potential for EBV-crossreactivity.