UNDERSTANDING THE ROLE OF 'THEMIS-SHP 1' INTERACTION IN T CELL RECEPTOR SIGNALING

Abstract

Themis has been shown to be important for T cell selection, for setting the threshold for positive versus negative selection. Themis interacts with the protein tyrosine phosphatase Shp1, a negative regulator of the T cell receptor signaling cascade. However, how Themis regulates Shp1 is still not clear. Here, using a very sensitive phosphatase assay on ex-vivo thymocytes, we have found that Themis enhances rather than inhibits Shp1 phosphatase activity. The regulation of Shp1 activity by Themis is found in thymocytes, but not in peripheral T cells, which might be due to differences in the relative abundance of the two proteins in thymus vs. periphery. Themis modulates Shp1 activity in response to TCR stimuli of different strengths. Surprisingly, there is redundancy between Shp1 and Shp2 to interact with Themis; in the absence of Shp1 in thymocytes, Themis interacts with Shp2 which leads to almost normal thymic development in Shp1 conditional knockout mice.