Themis releases the brakes on TCR signaling during thymocyte selection by disabling SHP-1

In this issue of Nature Immunology,Choi and colleagues1 identify a key function of the T cell-specific protein thymocyte-expressed molecule involved in selection(THEMIS)in T cell development.They demonstrate that the two structural CABIT(cysteine-containing all beta in THEMIS)modules contained in this protein are able to directly bind to the phosphotyrosine-phosphatase(PTP)domain of SHP-1(Src homology region 2 domain-containing phosphatase-1)and inhibit its phosphatase activity by increasing the susceptibility of its catalytic site to oxidation.