Quantitating Protein Synthesis, Degradation, and Endogenous Antigen Processing
Open accessAbstract
Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The density of MHC epitopes presented on the cell surface correlates with the amount of intracellular protein detected at a defined time point.
“Previous studies reported that the density of MHC epitopes presented on the cell surface correlates with the amount of intracellular protein detected at a defined time point.47”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 16
- [2]2. Antón, L.C. ∙ Yewdell, J.W. ∙ Bennink, J.R. MHC class I-associated peptides produced from endogenous gene products with vastly different efficiencies J. Immunol. 1997; 158:2535-2542 PubMed Google Scholar
- [3]3. Antón, L.C. ∙ Snyder, H.L. ∙ Bennink, J.R. ... Dissociation of proteasomal degradation of biosynthesized viral proteins from generation of MHC class I-associated antigenic peptides J. Immunol. 1998; 160:4859-4868 PubMed Google Scholar
- [4]4. Antón, L.C. ∙ Schubert, U. ∙ Bacik, I. ... Intracellular localization of proteasomal degradation of a viral antigen J. Cell Biol. 1999; 146:113-124 Crossref Scopus (194) PubMed Google Scholar
- [5]5. Buttgereit, F. ∙ Brand, M.D. ∙ Muller, M. ConA induced changes in energy metabolism of rat thymocytes Biosci. Rep. 1992; 12:109-114 Crossref Scopus (11) PubMed Google Scholar
- [6]6. Cascio, P. ∙ Hilton, C. ∙ Kisselev, A.F. ... 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide EMBO J. 2001; 20:2357-2366 Crossref Scopus (271) PubMed Google Scholar
- [7]7. Gagnon, E. ∙ Duclos, S. ∙ Rondeau, C. ... Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages Cell. 2002; 110:119-131 Full Text Full Text (PDF) Scopus (586) PubMed Google Scholar
- [8]8. Heim, R. ∙ Cubitt, A.B. ∙ Tsien, R.Y. Improved green fluorescence Nature. 1995; 373:663-664 Crossref Scopus (1562) PubMed Google Scholar
- [9]9. Hershko, A. ∙ Ciechanover, A. The ubiquitin system Annu. Rev. Biochem. 1998; 67:425-479 Crossref Scopus (7258) PubMed Google Scholar
- [10]10. Khan, S. ∙ de Giuli, R. ∙ Schmidtke, G. ... Cutting edgeneosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein J. Immunol. 2001; 167:4801-4804 PubMed Google Scholar
- [11]11. Kisselev, A.F. ∙ Akopian, T.N. ∙ Woo, K.M. ... The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation J. Biol. Chem. 1999; 274:3363-3371 Crossref Scopus (476) PubMed Google Scholar
- [12]12. Liljenstrom, H. ∙ von Heijne, G. Translation rate modification by preferential codon usageintragenic position effects J. Theor. Biol. 1987; 124:43-55 Crossref Scopus (67) PubMed Google Scholar
- [13]13. Malarkannan, S. ∙ Goth, S. ∙ Buchholz, D.R. ... The role of MHC class I molecules in the generation of endogenous peptide/MHC complexes J. Immunol. 1995; 154:585-598 PubMed Google Scholar
- [14]14. Montoya, M. ∙ del Val, M. Intracellular rate-limiting steps in MHC class I antigen processing J. Immunol. 1999; 163:1914-1922 PubMed Google Scholar
- [15]15. Nandi, D. ∙ Woodward, E. ∙ Ginsburg, D.B. ... Intermediates in the formation of mouse 20S proteasomesimplications for the assembly of precursor beta subunits EMBO J. 1997; 16:5363-5375 Crossref Scopus (160) PubMed Google Scholar
- [16]16. Nissen-Meyer, J. ∙ Eikhom, T.S. An excess of the small ribosomal subunits and a higher rate of turnover of the 60 S than of the 40 S ribosomal subunits in L cells grown in suspension culture J. Mol. Biol. 1976; 101:211-221 Crossref Scopus (11) PubMed Google Scholar
- [17]17. Palmiter, R.D. Quantitation of parameters that determine the rate of ovalbumin synthesis Cell. 1975; 4:189
Cited by
Sorted by citations
Towards a systems understanding of MHC class I and MHC class II antigen presentation
Neefjes, J., Jongsma, M. L. M., Paul, P., & Bakke, O. (2011) · Nature Reviews Immunology · doi:10.1038/nri3084 · Cited by 2,044 · see citing works
Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., K.Wansley, E., Camphausen, K., Luiten, R. M., de Ru, A. H., Neijssen, J., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052494 · Cited by 1,737 · see citing works
Dowling, R. J. O., Zakikhani, M., Fantus, I. G., Pollak, M., & Sonenberg, N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2310 · Cited by 933 · see citing works
Present yourself! by MHC class I and MHC class II molecules
Rock, K. L., Reits, E., & Neefjes, J. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.010 · Cited by 814 · see citing works
Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625 · see citing works
Energy regulation and neuroendocrine–immune control in chronic inflammatory diseases
Straub, R. H., Cutolo, M., Buttgereit, F., & Pongratz, G. (2010) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02218.x · Cited by 382 · see citing works
Self-citationOrlandini von Niessen, A. G., Poleganov, M. A., Rechner, C., Plaschke, A., Kranz, L. M., Fesser, S., Diken, M., Löwer, M., Vallazza, B., Beissert, T., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.12.011 · Cited by 365 · see citing works
Li, J. J., Bickel, P. J., & Biggin, M. D. (2014) · PeerJ · doi:10.7717/peerj.270 · Cited by 279 · see citing works
Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma
Wiśniewski, J. R., Ostasiewicz, P., Duś, K., Zielińska, D. F., Gnad, F., & Mann, M. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.44 · Cited by 248 · see citing works
Kuhn, A. N., Diken, M., Kreiter, S., Selmi, A., Kowalska, J., Jemielity, J., Darzynkiewicz, E., Huber, C., Türeci, Ö., & Sahin, U. (2010) · Gene Therapy · doi:10.1038/gt.2010.52 · Cited by 226 · see citing works
The brain and immune system prompt energy shortage in chronic inflammation and ageing
Straub, R. H. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.172 · Cited by 192 · see citing works
Pascolo, S. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.8.1285 · Cited by 152 · see citing works
Moura, G., Pinheiro, M., Arrais, J., Gomes, A. C., Carreto, L., Freitas, A., Oliveira, J. L., & Santos, M. A. S. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000847 · Cited by 107 · see citing works
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection
Rawson, P. M., Molette, C., Videtta, M., Altieri, L., Franceschini, D., Donato, T., Finocchi, L., Propato, A., Paroli, M., Meloni, F., et al. (2007) · Nature Medicine · doi:10.1038/nm1679 · Cited by 86 · see citing works
Energy metabolism and rheumatic diseases: from cell to organism
Spies, C. M., Straub, R. H., & Buttgereit, F. (2012) · Arthritis Research & Therapy · doi:10.1186/ar3885 · Cited by 47 · see citing works
Self-citationTripmacher, R., Gaber, T., Dziurla, R., Häupl, T., Erekul, K., Grützkau, A., Tschirschmann, M., Scheffold, A., Radbruch, A., Burmester, G., et al. (2008) · European Journal of Immunology · doi:10.1002/eji.200738047 · Cited by 46 · see citing works
Self-citationProctor, C. J., Tsirigotis, M., & Gray, D. A. (2007) · BMC Systems Biology · doi:10.1186/1752-0509-1-17 · Cited by 34 · see citing works
- Authors
- Princiotta, M. F., Finzi, D., Qian, S.-B., Gibbs, J., Schuchmann, S., Buttgereit, F., Bennink, J. R., & Yewdell, J. W.
- Affiliations
- National Institutes of Health (US)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Yewdell, Jonathan W.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 18
- Issue
- 3
- Pages
- 343-354
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2012324563
- Cited by
- 521
- References
- 0
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 20 · 2023: 12 · 2022: 16 · 2021: 24 · 2020: 10 · 2019: 19 · 2018: 23 · 2017: 11 · 2016: 19 · 2015: 15 · 2014: 23 · 2013: 20 · 2012: 27
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein synthesis, protein degradation, proteasome, MHC class I, antigen processing, viral peptides, ribosome, defective ribosomal products, dendritic cells, macrophages, T cell activation, L929 fibroblasts
- MeSH terms
- Animals, Antigen-Presenting Cells, Cell Line, Cysteine Endopeptidases, Energy Metabolism, Ligands, Multienzyme Complexes, Peptides, Proteins, Recombinant Fusion Proteins, Ribosomes, Protein Biosynthesis, Histocompatibility Antigens Class I, Antigen Presentation, Models, Immunological, Proteasome Endopeptidase Complex, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
