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Updated: Jun 14, 2026

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action
Avital Lev1, Michael F Princiotta, Damian Zanker
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Insights
Cells prevent immune surveillance bias by prioritizing defective ribosomal products (DRiPs) for peptide generation. Compartmentalizing DRiP peptide production ensures recognition of low-abundance proteins by CD8(+) T cells.
Area of Science:
- Immunology
- Molecular Biology
Background:
- MHC class I molecules present peptides to CD8(+) T cells for immune surveillance.
- Cellular proteins are abundant, risking biased immunosurveillance if all peptides are equally represented.
Purpose of the Study:
- To explain how T cells recognize peptides from low-abundance proteins.
- To investigate mechanisms preventing immune surveillance bias.
Main Methods:
- Analysis of peptide generation pathways.
- Investigating the role of defective ribosomal products (DRiPs) in peptide presentation.
- Studying the compartmentalization of peptide generation.
Main Results:
- Cells predominantly use DRiPs to generate peptides for MHC class I presentation.
- DRiP peptide generation is compartmentalized, preventing competition from abundant cytosolic peptides.
- This mechanism allows for the detection of peptides from low-abundance proteins.
Conclusions:
- Compartmentalization of DRiP peptide generation is crucial for effective immunosurveillance.
- This process explains the T cell repertoire's ability to detect peptides from diverse cellular and pathogen gene products, including those from low-abundance sources.
Abstract:
MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8(+) T cells. Cells typically express approximately 100,000 class I molecules, or approximately 1 per 30,000 cellular proteins. Given "one protein, one peptide" representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products.
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