The aryl hydrocarbon receptor, CIITA and HLA-II: who is watching the watchdog?

A recent paper by Jin et al. reveals an unexpected role of the Aryl Hydrocarbon Receptor (AHR), so far considered an environmental sensor. The authors demonstrate that AHR transactivates CIITA, thereby up-regulating antigen-presenting HLA-II molecules in cutaneous melanoma. In this commentary, we review the evidence supporting this original observation and discuss its potential biological implications. These findings suggest that the environmental exposome and HLA-II-mediated antigen presentation should be considered interconnected aspects of self-non-self-discrimination, with potentially important implications for tumor (immune) surveillance.