Major histocompatibility complex (MHC) class II antigens are almost exclusively expressed on immune cells such as dendritic cells and activated macrophages. It is known that their expression is necessary for the activation of lymphocytes and for a healthy immune response. The master transcription factor CIITA, which switches on class II MHC gene expression, must itself be regulated. In a Perspective, Mach discusses how this master transcription factor may be regulated by binding to the signaling molecule guanosine triphosphate (GTP) (as described in this issue by Harton et al .)