Sporadic Inclusion-Body Myositis (s-IBM) is the most common muscle disease in patients above the age of 50 years. It is an inflammatory myopathy mediated by sensitized, cytotoxic CD8+ T cells that clonally expand in situ and invade MHC-I-expressing muscle fibers. The antigen recognized by the T cells is unknown. The disease is progressive, resists the currently available immunotherapies and leads to wheelchair confinement. Applying therapeutic strategies with agents that deplete T cells clones and investigating the antigenic specificity of the endomysial T cells is expected to enhance our understanding of the cause of s-IBM and lead to clinical improvement. The present study is designed to: a) test in a pilot study the safety, T cell depletion of the endomysial T cells and clinical efficacy of the monoclonal antibody Alemtuzumab in 20 patients with s-IBM followed for 12 months by serial quantitative assessment of muscle strength; b) explore the spectrum of the antigens recognized by the T cells extracted from the muscle biopsy specimens by searching for immune dominant peptides using positional scanning synthetic combinational peptide libraries, before and after therapy; and c) determine the reciprocal relationship between clinical response and endomysial inflammatory mediators before and after treatment. It is anticipated that the study may lead to identification of putative antigens that trigger the disease, clarify the significance of the inflammation and amyloid deposits in muscle fiber injury and provide a novel therapy for s-IBM patients.