REGULATION OF T CELL RECEPTOR GENE DIFFERENTIATION

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DESCRIPTION: (Adapted from the applicant's abstract) All known vertebrates harbor three sets of lymphocytes, B cells, alpha/beta (ab) T cells, and gamma/delta (gd) T cells, defined by their respective antigen receptors. The role of gd T-cells in host protection and maintenance is poorly understood, and many studies aimed at resolving this have compared and contrasted gd T cells with the other two types of lymphocytes. Interestingly, emerging functional properties of gd T-cells suggest that they may share features hitherto regarded as B-cell-specific or ab T-cell-specific. In this application, studies are described that will continue our examination of gd T-cell development. Again, emerging information indicates that some gd T cells are highly similar to ab T cells, being derived from the same lineage, whereas others are B-cell like, even being extrathymically derived. The application lists seven specific aims, the success of which can confirm this "dual pathway" view of gd T-cell development and provide important mechanistic insight into how development is regulated. Such knowledge can significantly improve our basic depiction of T-cell development. In addition, it provides guidance as to how T-cell development might be experimentally manipulated in cases of autoimmunity, immunodeficiency, or transplant.