While signals delivered by the T cell antigen receptor (TCR) and other co-receptors play an essential role for early T cell development, it remains to be clarified as to how are these signals modulated intracellularly. We have identified that the proto-oncoprotein Cbl is a negative regulator for TCR signaling, and physiologically regulates the TCR signalling threshold during thymic selection. These results provide first evidence that proto-onco protein Cbl physiologically contributes to the thymic selection and establishment of the functional T cell population in mice. It has been technically difficult to simultaneously detect the activated T cells and their movement in vivo. We have established a reporter mouse line in which the activated IL-2 producing T cells can be readily monitored by a GFP marker inserted into its IL-2 gene locus. This mouse model provides us a powerful approach to non- destructively identify IL-2 producing T cells and follow their subsequent differentiation fate both in vitro and in vivo. - TCR signaling, adaptor molecule, Cbl, thymic selection, T cell development, IL-2 gene expression, GFP reporter, gene targeting.
