ArticleProceedings of the National Academy of Sciences of the United States of America2024
Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Haematopoietic Cells Deficient for Calreticulin or Expressing Its Oncogenic Variants Maintain Functional Antigen Presentation.Journal of cellular and molecular medicine · 2026Article
- Review
- Quantitative nanoscale imaging shows peptide-MHC I complexes are monomeric and spatially regulated in human dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Peptide Loading Complex in Cancer: From Peptide Translocation, Editing, and Loading into MHC-I to a Potential Therapeutic Target.Current medical science · 2026Review
- Aberrant SUMOylation Restricts the Targetable Cancer Immunopeptidome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comparative analysis of pan MHC‑I epitopes immunoreactivity on Hantaan virus nucleocapsid protein.International journal of molecular medicine · 2026Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- IL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer.Molecular cancer · 2025Article
- CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The potential applications of peptide-loading complex in cancer treatment.Frontiers in immunology · 2025Review
- Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
Antigen presentation via major histocompatibility complex class I (MHC-I) molecules is essential for surveillance by the adaptive immune system. Central to this process is the peptide-loading complex (PLC), which translocates peptides from the cytosol to the endoplasmic reticulum and catalyzes peptide loading and proofreading of peptide-MHC-I (pMHC-I) complexes. Despite its importance, the impact of individual PLC components on the presented pMHC-I complexes is still insufficiently understood. Here, we used stoichiometrically defined antibody-nanobody complexes and engineered soluble T cell receptors (sTCRs) to quantify different MHC-I allomorphs and defined pMHC-I complexes, respectively. Thereby, we uncovered distinct effects of individual PLC components on the pMHC-I surface pool. Knockouts of components of the PLC editing modules, namely tapasin, ERp57, or calreticulin, changed the MHC-I surface composition to a reduced proportion of HLA-A*02:01 presentation compensated by a higher ratio of HLA-B*40:01 molecules. Intriguingly, these knockouts not only increased the presentation of suboptimally loaded HLA-A*02:01 complexes but also elevated the presentation of high-affinity peptides overexpressed in the cytosol. Our findings suggest that the components of the PLC editing module serve a dual role, acting not only as peptide proofreaders but also as limiters for abundant peptides. This dual function ensures the presentation of a broad spectrum of antigenic peptides.
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