Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class I molecules?
Abstract
MHC class I molecules predominantly bind to peptides derived from a cytosolic pool of polypeptides. Little is known about the nature of the polypeptides that serve as substrates for peptidogenic cytosolic proteases. We propose that a significant source of self and viral peptides are defective ribosomal products (DRiPs), which consist of prematurely terminated polypeptides and misfolded polypeptides produced from translation of bona fide mRNAs in the proper reading frame. DRiPs are produced entropically, due to the inevitable imperfections inherent to protein synthesis or folding. To accelerate recognition of cells harboring intracellular parasites such as viruses, DRiP formation may be enhanced by changes in the cellular physiology induced by infection or by exposure of cells to cytokines released at the site of inflammation.
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The observations that MHC epitope density correlates with intracellular protein and that epitope production occurs without detectable full-length protein are not contradictory and may be explained by defective ribosomal products (DriPs) being quickly processed into peptides and contributing significantly to MHC-associated epitopes.
“These observations are not contradictory but may be explained by the fact that in addition to steady state protein levels, defective ribosomal products (DriPs) such as unfinished or misfolded proteins are quickly processed into peptides and contribute significantly to MHC-associated epitopes.49”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [49]
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- Authors
- Yewdell, J. W., Antón, L. C., & Bennink, J. R.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-09-01
- Volume
- 157
- Issue
- 5
- Pages
- 1823-1826
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1925735392
- Cited by
- 450
- References
- 0
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 12 · 2023: 17 · 2022: 17 · 2021: 20 · 2020: 26 · 2019: 18 · 2018: 17 · 2017: 12 · 2016: 15 · 2015: 20 · 2014: 16 · 2013: 16 · 2012: 20
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- defective ribosomal products, MHC class I, antigenic peptides, cytosolic proteases, early termination, misfolded proteins, viral peptides, self-peptides, intracellular parasites, cytokines, inflammation, immune recognition
- MeSH terms
- Animals, Antigens, Humans, Peptide Biosynthesis, Peptides, Ribosomal Proteins, Histocompatibility Antigens Class I, Antigen Presentation
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