Figure 1.

Expression of THEMIS in preselection thymocytes promotes TCR-dependent signaling by attenuating the phosphatase activity of SHP-1. (a) Binding of self-p/MHCs to low-affinity TCRs expressed on the surface of CD4⁺/CD8⁺ DP thymocytes leads to the recruitment to phosphorylated LAT to a multimolecular complex containing THEMIS, growth factor receptor-bound 2 and SHP-1. THEMIS inhibits SHP-1 activity by increasing its susceptibility to ROS produced following T-cell activation, leading to the stage-specific enhancement of TCR signaling and allowing thymocytes to proceed along the differentiation process. (b) In stimulated Themis^−/− thymocytes, SHP-1 recruited to LAT is in its active state. The subsequent dephosphorylation of initiating kinases ZAP-70 and Lck dampens TCR signaling, impairing positive selection.