The 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.
