Figure 1: Different mechanisms regulate PD-1 expression in T cells. (1) NFATc1 or c-Fos induces PD-1 expression upon stimulation, while T-bet represses transcription of PD-1 (black lines). (2) HIV Nef induced PD-1 transcription is dependent on p38/MAPK activation. Hepatitis B Core Antigen (HBcAg) induces PD-1 expression on T cells, which depends on the phosphorylation of JNK, ERK and AKT (blue lines). (3) IFN-α promotes the induction and maintenance of PD-1 expression through an association of IFNresponsive factor 9 (IRF9) to the IFN stimulation response element on the pdcd1 promoter (green lines). (4) DNA demethylation at the pdcd1 promoter increases PD-1 expression (pink line).