To produce transgenic mice which express T cell receptors specific for (IRBP).

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DESCRIPTION (provided by applicant): Autoimmune posterior uveitis is a T cell mediated autoimmune disease characterized by mononuclear infiltrate into the retina and irreversible photoreceptor destruction. While the cause is unknown, experimental autoimmune uveitis (EAU) can be induced in mice through immunization with interphotoreceptor retinoid binding protein (IRBP). Numerous studies in the EAU field as well as other autoimmune disease models suggest that the primary cause of autoimmune disease is a failure of immune tolerance mechanisms. T cell receptor (TCR) transgenic mice have provided, and continue to provide, a wealth of important information on mechanisms of tolerance induction as well as mechanisms of autoimmune tissue destruction, particularly in the multiple sclerosis and diabetes fields. In this exploratory/developmental research grant application, the applicant proposes to develop TCR transgenic mice with specificity for IRBP as a new model for EAU. The applicant has successfully cloned full length cDNAs encoding the alpha and beta chains of the TCR from three IRBP specific T cell clones, and is in the process of cloning the receptor genes from two other T cell clones. In the first aim, the applicant will generate two lines of transgenic mice from two different T cell clones. In the second aim, the applicant will perform the initial characterization of the lines in order to establish them as useful models for EAU. These mice will be made available to the uveitis research community and create valuable new models for uveitis research. Studies using these mice may lead to new therapies for the treatment of uveitis. PUBLIC HEALTH RELEVANCE: This project will generate new transgenic mouse models for autoimmune uveitis, a severe sight threatening autoimmune disease. Similar mouse models have been produced for multiple sclerosis and diabetes and have been responsible for dramatic advances in those fields. These mice will be made available to the research community and thus foster new research into cures or treatment for autoimmune uveitis.