ArticleProceedings of the National Academy of Sciences of the United States of America2011
An antigenic peptide produced by reverse splicing and double asparagine deamidation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 129 citations in OpenAlex.
- PepQueryMHC: rapid and comprehensive tumor antigen prioritization from immunopeptidomics data.Genome biology · 2025Article
- Immunopeptidomics for autoimmunity: unlocking the chamber of immune secrets.NPJ systems biology and applications · 2025Review
- Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing.Nature communications · 2024Article
- Non-mutational neoantigens in disease.Nature immunology · 2024Review
- Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen.iScience · 2023Article
- 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
- Neoantigens: promising targets for cancer therapy.Signal transduction and targeted therapy · 2023Review
- Recent advances in immunopeptidomic-based tumor neoantigen discovery.Advances in immunology · 2023Article
- What do cancer-specific T cells 'see'?Discovery immunology · 2023Review
- Boosting Antitumor Immunity with an Expanded Neoepitope Landscape.Cancer research · 2022Review
- Review
- Sources of Cancer Neoantigens beyond Single-Nucleotide Variants.International journal of molecular sciences · 2022Review
- 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
- Predicting the Success of Fmoc-Based Peptide Synthesis.ACS omega · 2022Article
- Article
- Therapeutic Vaccines against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens?International journal of molecular sciences · 2022Review
- Identification of tumor antigens with immunopeptidomics.Nature biotechnology · 2022Review
- Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
A variety of unconventional translational and posttranslational mechanisms contribute to the production of antigenic peptides, thereby increasing the diversity of the peptide repertoire presented by MHC class I molecules. Here, we describe a class I-restricted peptide that combines several posttranslational modifications. It is derived from tyrosinase and recognized by tumor-infiltrating lymphocytes isolated from a melanoma patient. This unusual antigenic peptide is made of two noncontiguous tyrosinase fragments that are spliced together in the reverse order. In addition, it contains two aspartate residues that replace the asparagines encoded in the tyrosinase sequence. We confirmed that this peptide is naturally presented at the surface of melanoma cells, and we showed that its processing sequentially requires translation of tyrosinase into the endoplasmic reticulum and its retrotranslocation into the cytosol, where deglycosylation of the two asparagines by peptide-N-glycanase turns them into aspartates by deamidation. This process is followed by cleavage and splicing of the appropriate fragments by the standard proteasome and additional transport of the resulting peptide into the endoplasmic reticulum through the transporter associated with antigen processing (TAP).
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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.