The search for autoantigens and molecular mimics in Multiple Sclerosis
Mireia Sospedra Ramos
CRPP Multiple Sclerosis, U. Zurich (Switzerland)
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that develops in genetically susceptible individuals, likely requires environmental triggers and involves several pathomechanisms. This complex etiology and pathogenesis translate into as yet poorly understood disease heterogeneity that often jeopardizes clinical care. MS is considered a T cell-mediated disease. However, the autoantigens and molecular mimics triggering the autoimmune response in MS remain incompletely understood, most likely because the limited access of brain-infiltrating T cells. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified an autoantigen that is recognized by cerebrospinal fluid-infiltrating CD4+ T cells from HLA-DRB3*-positive patients. The identification of autoantigens and molecular mimics targeted by pathogenic T cells not only can improve our understanding of MS pathogenesis, its diagnosis and classification but also the development of antigen-specific immunotherapies.