Autophagy‐dependent regulation of MHC‐I molecule presentation

Abstract

AbstractThe major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I‐restricted CD8+ T lymphocytes to elicit an effective immune response. The conventional antigen‐processing pathway for MHC‐I presentation depends on proteasome‐mediated peptide generation and peptide loading in the endoplasmic reticulum by members of the peptide loading complex. Recent discoveries in this field highlight the role of alternative MHC‐I peptide loading and presentation pathways, one of them being autophagy. Autophagy is a cell‐intrinsic degradative pathway that ensures cellular homoeostasis and plays critical roles in cellular immunity. In this review article, we discuss the role of autophagy in MHC class I‐restricted antigen presentation, elucidating new findings on the crosstalk of autophagy and ER‐mediated MHC‐I peptide presentation, dendritic cell‐mediated cross‐presentation and also mechanisms governing immune evasion. A detailed molecular understanding of the key drivers of autophagy‐mediated MHC‐I modulation holds promising targets to devise effective measures to improve T cell immunotherapies.