PTPN22 and autoimmune disease: Taken together with data from mouse studies,25 these observations suggest that a principle function of PTPN22 is to limit activation of weakly self-reactive T cells and that in the absence of PTPN22, or in the presence of the disease-associated R619W/R620W variant, increased TCR signaling and activation of such cells is permitted, contributing to induction of autoimmune disease.