ArticleMolecular & cellular proteomics : MCP2021
Are There Indeed Spliced Peptides in the Immunopeptidome?
Article in Molecular & cellular proteomics : MCP, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Methods for Isolating and Analyzing the HLA Class I Immunopeptidome.Methods in molecular biology (Clifton, N.J.) · 2026Article
- PepQueryMHC: rapid and comprehensive tumor antigen prioritization from immunopeptidomics data.Genome biology · 2025Article
- Proteasome-derived peptides: separating the trash from the recycling.Trends in biochemical sciences · 2025Review
- Challenges in developing personalized neoantigen cancer vaccines.Nature reviews. Immunology · 2024Review
- Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing.Nature communications · 2024Article
- Game of Omes: ribosome profiling expands the MHC-I immunopeptidome.Current opinion in immunology · 2023Review
- Large-Scale Immunopeptidome Analysis Reveals Recurrent Posttranslational Splicing of Cancer- and Immune-Associated Genes.Molecular & cellular proteomics : MCP · 2023Article
- Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.Seminars in immunology · 2023Review
- InvitroSPI and a large database of proteasome-generated spliced and non-spliced peptides.Scientific data · 2023Article
- iBench: A ground truth approach for advanced validation of mass spectrometry identification method.Proteomics · 2023Article
- An unexplored angle: T cell antigen discoveries reveal a marginal contribution of proteasome splicing to the immunogenic MHC class I antigen pool.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Immunopeptidomics: Reading the Immune Signal That Defines Self From Nonself.Molecular & cellular proteomics : MCP · 2022Article
- Article
- Neo-Splicetopes in Tumor Therapy: A Lost Case?Frontiers in immunology · 2022Review
- Mechanistic diversity in MHC class I antigen recognition.The Biochemical journal · 2021Review
- Review
- Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.Proteomics · 2021Review
- Commentary: Are There Indeed Spliced Peptides in the Immunopeptidome?Molecular & cellular proteomics : MCP · 2021Article
- Is the Immunopeptidome Getting Darker?: A Commentary on the Discussion around Mishto et al., 2019.Frontiers in immunology · 2021Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
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Abstract
The claims that a large fraction of the immunopeptidome is composed of spliced major histocompatibility complex (MHC) peptides have stirred significant excitement and raised controversy. Here, I suggest that there are likely no spliced peptides in the immunopeptidome, and if they exist at all, they are extremely rare. I base this claim on both biochemical and bioinformatics considerations. First, as a reactant in normal proteolytic reactions, water will compete with transpeptidation, which has been suggested as the mechanism of peptide splicing. The high mobility and abundance of water in aqueous solutions renders transpeptidation very inefficient and therefore unlikely to occur. Second, new studies have refuted the bioinformatics assignments to spliced peptides of most of the immunopeptidome MS data, suggesting that the correct assignments are likely other canonical, noncanonical, and post-translationally modified peptides. Therefore, I call for rigorous experimental methodology using heavy stable isotope peptides spiking into the immunoaffinity-purified mixtures of natural MHC peptides and analysis by the highly reliable targeted MS, to claim that MHC peptides are indeed spliced.
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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.