REGULATION OF RECEPTORS ON T-LYMPHOCYTES

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Origin of B and T cells from a common precursor suggests that there might be overlap in the transcriptional regulation of genes, particularly those expressed soon after divergence of the 2 lineages. Analysis of factors regulating early lymphoid gene expression should provide insights into the signals leading to B and T cell differentiation. The TCR beta gene is expressed early during T cell ontogeny and may share regulatory features with the immunoglobulin mu heavy chain gene. The IL- 2Ralpha gene is induced upon T cell activation via a sequence element homologous to the NF-kB binding site, originally identified in the immunoglobulin k light chain gene enhancer. The immediate goals of the experiments outlined in this application are to define (by transfection and transgenic mouse analysis) the sequence elements required for appropriate expression of the TCR-beta and IL-2Ralpha genes and subsequently identified the trans-acting factors interacting with these sequences. These studies are expected to place us in a strong position to probe lymphoid development by identifying factors that are critical in turning genes on or off at different stages of B and T cell development.