Figure 1.

PTPN22 function in T cells. (A) PTPN22^620R and PEP^619R are negative regulators of TCR signaling in T cells where they dephosphorylate/deactivate signaling intermediates and reduce signaling from the TCR to the nucleus. (B) The PTPN22^620W gain-of-function hypothesis. In this scenario, PTPN22^620W is more active and dephosphorylates signaling intermediates at an increased rate compared to PTPN22^620R. This blunts TCR signaling compared to PTPN22^620R and reduces T cell response. (C) The PTPN22^620W and PEP^619W loss-of-function hypothesis. In this scenario, PTPN22^620W/PEP^619W are less efficient at dephosphorylating TCR signaling intermediates compared to PTPN22^620R/PEP^619R. This allows more signal from the TCR to reach the nucleus and increases T cell response to TCR stimulation.