The broad, long term objective of this application is to gain insight into the physiological role of gammadelta TCR+ T cell subsets. The studies propose include the following specific aims: 1. To characterize further the murine repertoire of gammadelta TCRs expressed during T cell development in the thymus. We will extend a collection of gammadelta+ thymocyte hybridomas using a novel T cell fusion line which is permissive for the surface expression of gammadelta: The gammadelta receptors will be analyzed, using PCR technology, cDNA cloning and sequencing, and two-dimensional gel electrophoresis of receptor proteins. 2. To test the concept that the entire gammadelta+ cell population, or large parts of it, consists of specialized local subsets, each of which bears one or a group of characteristic receptor molecules. We will purify gammadelta+ cells from different organs, including different lymphoid organs and lungs. We will analyze gamma and delta V gene expression in these cells. This study should provide us with some insight into the general organization of the gammadelta+ T cell population. 3. To study the reactivity of gammadelta+ T cells with alloantigens and self-MHC class I determinants. To detyermine frequencies of alloreactive gammadelta+ cells, we will test alloantigens as stimulators with a large panel of unselected gammadelta+ and alphabeta + hybridomas. To evaluate the possible role of MHC class I molecules, we will study the development of normal gammadelta cells in mice chronically injected with anti MHC class I antibodies. 4. To generate a alphabeta-gammadelta+ mouse model. We will use a new pan-specific anti-alphabeta antibody. Newborn animals will be chronically injected with this antibody to selectively suppress the development of alphabeta+ T cells. These mice will be studied as potential models for gammadelta cell funciton in vivo.
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