Antigen presentation unfolded: identifying convergence points between the UPR and antigen presentation pathways.

Area of Science:

• Cellular Biology
• Immunology

Background:

• The unfolded protein response (UPR) is a cellular stress response crucial for maintaining endoplasmic reticulum (ER) homeostasis.
• Emerging evidence links UPR to diverse cellular functions beyond its canonical role, including innate immunity and antigen presentation.

Purpose of the Study:

• To elucidate the intricate mechanisms by which the UPR influences both MHC-I and MHC-II antigen presentation pathways.
• To review the direct and indirect interactions between UPR signaling and antigen processing and presentation.

Main Methods:

• Literature review and synthesis of existing research on UPR, ER stress, innate immunity, and antigen presentation.
• Analysis of molecular pathways connecting UPR signaling components to MHC-I and MHC-II processing and surface expression.

Main Results:

• The UPR directly modulates the expression and function of key proteins involved in antigen processing and loading onto MHC molecules.
• Indirect effects of UPR on antigen presentation include alterations in ER-associated degradation (ERAD) and immune cell signaling pathways.
• UPR activation can significantly impact the repertoire of peptides presented by MHC-I and MHC-II, influencing adaptive immune responses.

Conclusions:

• The UPR is a critical regulator with far-reaching implications for immune surveillance and response.
• Understanding UPR's role in antigen presentation offers new insights into immune evasion strategies and potential therapeutic targets.