ArticleImmunogenetics2005
The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage.
Article in Immunogenetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 273 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
273 citing papers in PubMed, 1 synthesis or guideline pooled it, 487 citations in OpenAlex.
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- Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2017Trial
- TrambaHLApan: A Transformer and Mamba-based Neoantigen Prediction Method Considering both Antigen Presentation and Immunogenicity.Interdisciplinary sciences, computational life sciences · 2026Article
- AI-driven neoantigen identification: a comprehensive review from somatic variant calling to T cell recognition.Journal of translational medicine · 2026Review
- Innovative multi-epitope vaccine engineering for dual protection against Salmonella and Shigella leveraging FliC flagellin protein adjuvant properties: an immunoinformatics-based approach.Journal of translational medicine · 2026Article
- Immunopeptidomics-guided identification of functional neoantigens in non-small cell lung cancer.NPJ precision oncology · 2026Article
- Advances in predicting T cell epitope recognition for cancer immunotherapy.Nature cancer · 2026Review
- Identification and prioritisation of tumour antigen candidates from 79 glioblastoma transcriptomes.Cancer immunology, immunotherapy : CII · 2026Article
- Decoding immunotherapy response through computational modeling.Nature communications · 2026Review
- In silico design and immunoinformatics evaluation of a multi-epitope vaccine targeting SEPT9 for gastrointestinal adenocarcinomas.BMC immunology · 2026Article
- In Silico Design and Evaluation of TcGAPDH as a Vaccine Against Chagas Disease: A Reverse Vaccinology Approach.Acta parasitologica · 2026Article
- Substrate secondary structure is associated with proteasomal cleavage propensity.Frontiers in bioinformatics · 2026Article
- Computational Methods for Cancer Neoantigen Prediction.Methods in molecular biology (Clifton, N.J.) · 2026Article
- BeitAI-pHLA: Multiallele Peptide-HLA Class I Binding Prediction Using Protein Language Model and Multi-Instance Learning.Computational and structural biotechnology journal · 2026Article
- AI-powered mapping of tumor immunity for optimized mRNA vaccine engineering.Frontiers in oncology · 2026Review
- Preclinical Assessment of HLA-A*02:01-Restricted PSMA and STEAP1 Epitopes for Peptide-Based Immunotherapy in Prostate Cancer.Drug design, development and therapy · 2026Article
- Article
- Cleaving Expectations: A Review of Proteasome Functional and Catalytic Diversity.Biomolecules · 2025Review
- Rapid-Turnaround Co-Administration of mRNA-Based MHC-I and MHC-II-Restricted Neoantigens Enhances Immune Responses of Antigen-Specific CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
213 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Cytotoxic T cells (CTLs) perceive the world through small peptides that are eight to ten amino acids long. These peptides (epitopes) are initially generated by the proteasome, a multi-subunit protease that is responsible for the majority of intra-cellular protein degradation. The proteasome generates the exact C-terminal of CTL epitopes, and the N-terminal with a possible extension. CTL responses may diminish if the epitopes are destroyed by the proteasomes. Therefore, the prediction of the proteasome cleavage sites is important to identify potential immunogenic regions in the proteomes of pathogenic microorganisms (or humans). We have recently shown that NetChop, a neural network-based prediction method, is the best method available at the moment to do such predictions; however, its performance is still lower than desired. Here, we use novel sequence encoding methods and show that the new version of NetChop predicts approximately 10% more of the cleavage sites correctly while lowering the number of false positives with close to 15%. With this more reliable prediction tool, we study two important questions concerning the function of the proteasome. First, we estimate the N-terminal extension of epitopes after proteasomal cleavage and find that the average extension is relatively short. However, more than 30% of the peptides have N-terminal extensions of three amino acids or more, and thus, N-terminal trimming might play an important role in the presentation of a substantial fraction of the epitopes. Second, we show that good TAP ligands have an increased chance of being cleaved by the proteasome, i.e., the specificity of TAP has evolved to fit the specificity of the proteasome. This evolutionary relationship allows for a more efficient antigen presentation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.