Physiological T cell activation, including that induced by CD19-ReTARGTPR, is tightly regulated, and the highly layered architecture of negative T cell regulation, including transmembrane adaptors (PAG and SIT), phosphatases (SHP-1 and PTEN), kinases (DGKs), and E3 ligases, prevents the overstimulation of T cells, which would result in autoimmunity or early T cell exhaustion (reviewed in [20]). Here, PTEN is linked to Autoimmunity.