Immediate hypersensitivity or allergy is the most widespread immunological disorder in humans. We have recently developed a mouse model of allergic conjunctivitis to cat dander (Fel dl), and characterized the T helper responses in susceptible animals. Approximately 25% of the world's population suffer from allergies; with ocular symptoms contributing a significant proportion of the discomfort and patient care costs associated with allergic disease. There is considerable interest among ophthalmologists for the development of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye. A novel and promising approach to management of ongoing allergic disease is that of peptide immunotherapy. Identification of defined T cell epitopes containing peptides, based on the primary structure of major allergens may provide an effective tool for modification of human immediate hypersensitivity to allergens. Since functional and biochemical studies have demonstrated that the generation of T cell responses depends upon antigen receptors on T cells (TCR) recognizing peptide fragments of foreign proteins associated with products of the major histocompatibility complex (MHC), that are expressed on the membranes of accessory cells, any examination of T cell epitopes must also include MHC analysis. Therefore, the goal of this proposal is to use our mouse model of allergic conjunctivitis to clearly define the molecular interaction in the ternary complex of immunodominant peptide, the MHC on the antigen presenting cell (APC), and the T cell receptor. After we have define the specific T cell/peptide/APC interaction, we will use this information to develop a novel T cell vaccine my making an antigenized MHC-Ig chimera, and then to test this T cell vaccine in our mouse model of allergic conjunctivitis.
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