Abstract
Direct MHC class I antigen presentation is a necessary step to identify cells for elimination by cytotoxic CD8+ T cells. Antigenic peptides may originate from host-derived unnecessary or “retired” proteins as well as defective ribosomal products (DRiPs). DRiPs are newly synthesized polypeptides incapable of attaining a stable configuration and are thus rapidly degraded. The balance between protein synthesis and degradation, key processes to antigenic peptide generation, are likely influenced by the unfolded protein response (UPR). The UPR is a cellular response designed to alleviate the toxic accumulation of unfolded proteins in the endoplasmic reticulum. Several disease conditions requiring CD8+ T cell responses such as viral infection and tumorigenesis are known to influence the UPR. In this study, we utilized small inhibitory molecules targeting individual branches of the UPR to investigate the effect on both global MHC class I levels and the presentation of peptides from both DRiP and non-DRiP sources. Inhibition of the IRE1α signaling pathway but not the PERK pathway reduced total MHC class I levels. Presentation of peptides derived from DRiPs was unaffected by inhibiting either branch of the UPR. These data suggest that specific perturbations to the UPR has the capacity to alter host antigen presentation of peptides from particular peptide sources.