Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability

The strength of the signal produced by the T cell receptor (TCR) in response to self-antigen determines whether an immature thymocyte undergoes positive selection and matures into a T cell or negative selection and is eliminated to avoid autoreactivity. Both selection processes require the protein Themis1. By examining the effects of either loss or overexpression of Themis1 in thymocytes in mice, Zvezdova et al . determined that Themis1 enhances the activity of the guanine nucleotide exchange factor Vav1 and the stability of the TCR-associated adaptor protein Grb2, thus enabling TCR signaling. These data suggest that, although Themis1 also recruits a phosphatase to the TCR complex, the primary role for Themis1 is to enhance rather than inhibit TCR signaling to promote thymocyte development.