Optineurin modulates mTORC2/AKT/STAT3 signaling to control MHC II expression and adaptive immunity against HSV-1

Improving antigen presentation is key to better vaccine strategies and more robust immune responses. Here, we show that OPTN, an autophagy receptor traditionally involved in protein recycling, unexpectedly stabilizes RICTOR (mTORC2), a crucial step in enhancing MHC-II surface expression in dendritic cells.

OPTN regulates the AKT/mTOR/STAT3 pathway, with AKT2 isoform playing a central role. Using scRNA-seq and transgenic mouse models, we identify the mechanistic details of this pathway. Dysregulation impairs antigen presentation, weakening immunity and vaccine efficacy.