ER stress affects processing of MHC class I-associated peptides

Area of Science:

• Immunology
• Cellular Biology
• Molecular Biology

Background:

• Viral infections and cancer induce endoplasmic reticulum (ER) stress.
• Cells activate the unfolded protein response (UPR) to manage ER stress.
• UPR influences major histocompatibility complex class I (MHC I)-peptide presentation.

Purpose of the Study:

• To investigate the impact of UPR on MHC I-peptide presentation.
• To determine how ER stress affects the presentation of peptides derived from different cellular compartments.

Main Methods:

• EL4 cells were subjected to ER stress using palmitate or glucose deprivation.
• Assessed global MHC I expression and presentation of a specific peptide (SIINFEKL).
• Analyzed MHC I mRNA levels, intracellular protein amounts, and peptide supply.

Main Results:

• UPR reduced surface MHC I expression but not mRNA or total intracellular protein.
• Impaired MHC I-peptide presentation resulted from reduced peptide supply due to inhibited protein synthesis.
• ER-derived peptides were less affected than cytosol-derived peptides due to increased stability of cytosolic proteins.

Conclusions:

• ER stress significantly impairs MHC I-peptide presentation.
• Differential regulation of ER- vs. cytosol-derived peptides occurs during ER stress.
• ER stress impacts adaptive immune recognition by altering MHC I-peptide presentation cues.