Thyroid associated ophthalmopathy ((TAO)) is one of the most common organ specific autoimmune disorders and is found most frequently in patients with Graves' hyperthyroidism. About 5% of patients with TAO will develop disfiguring and sight threatening disease. A 64 kDa eye muscle antigen has been identified as a target of autoantibodies associated with this disease. I this study we plan to clone the 64 kDa eye muscle protein using oligonucleotides prepared on the basis of protein microsequence information as molecular probes. In addition, antibody and T lylmphocyte epitopes will be mapped to fragments of the full length protein to identify the most reactive epitopes including those which best predict the development of ophthalmopathy patients with Graves' disease. A good understanding of the molecular nature of the 64 kDa eye muscle and thyroid shared autoantigen and the significance of autoantibody and T lymphocyte reactivity against it will help clarify the role of this membrane protein in the pathogenesis of TAO as well as providing the basis for future therapy and prevention of the eye disorder.