ArticleThe Journal of biological chemistry2016
A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- T cell receptors equipped with ICOS provide T cells with durable anti-tumor response.Molecular cancer · 2026Article
- Position-5-driven reorientation of an immunodominant HLA-A*24:02 SARS-CoV-2 epitope drives universal T cell escape.JCI insight · 2026Article
- Computational design of orthogonal TCR α/β interfaces for dual-TCR therapeutics.bioRxiv : the preprint server for biology · 2026Article
- Jembrana disease in Indonesia: An updated review.Open veterinary journal · 2025Review
- Identification and Analysis of Anticancer Therapeutic Targets from the Polysaccharide Krestin (PSK) and Polysaccharopeptide (PSP) Using Inverse Docking.Molecules (Basel, Switzerland) · 2024Article
- A Bibliometric Analysis of Melanoma Treated with Vaccinations Research from 2013 to 2023: A Comprehensive Review of the Literature.Vaccines · 2023Article
- Biomaterials Facilitating Dendritic Cell-Mediated Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Therapeutic high affinity T cell receptor targeting a KRASNature communications · 2022Article
- Article
- Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.European journal of immunology · 2022Article
- Mooring Stone-Like ArgJournal of virology · 2022Article
- Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.Discovery immunology · 2022Review
- Haptenation of Macrophage Migration Inhibitory Factor: A Potential Biomarker for Contact Hypersensitivity.Frontiers in toxicology · 2022Article
- Physicochemical Heuristics for Identifying High Fidelity, Near-Native Structural Models of Peptide/MHC Complexes.Frontiers in immunology · 2022Article
- Synthetic Peptides with Inadvertent Chemical Modifications Can Activate Potentially Autoreactive T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Structures suggest an approach for converting weak self-peptide tumor antigens into superagonists for CD8 T cells in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- T-Cell Immunotherapy for Pediatric High-Grade Gliomas: New Insights to Overcoming Therapeutic Challenges.Frontiers in oncology · 2021Review
- Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate Cancer: An In Silico Approach.Cell biochemistry and biophysics · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Human CD8(+) cytotoxic T lymphocytes can mediate tumor regression in melanoma through the specific recognition of HLA-restricted peptides. Because of the relatively weak affinity of most anti-cancer T-cell receptors (TCRs), there is growing emphasis on immunizing melanoma patients with altered peptide ligands in order to induce strong anti-tumor immunity capable of breaking tolerance toward these self-antigens. However, previous studies have shown that these immunogenic designer peptides are not always effective. The melanocyte differentiation protein, glycoprotein 100 (gp100), encodes a naturally processed epitope that is an attractive target for melanoma immunotherapies, in particular peptide-based vaccines. Previous studies have shown that substitutions at peptide residue Glu(3) have a broad negative impact on polyclonal T-cell responses. Here, we describe the first atomic structure of a natural cognate TCR in complex with this gp100 epitope and highlight the relatively high affinity of the interaction. Alanine scan mutagenesis performed across the gp100(280-288) peptide showed that Glu(3) was critically important for TCR binding. Unexpectedly, structural analysis demonstrated that the Glu(3) → Ala substitution resulted in a molecular switch that was transmitted to adjacent residues, abrogating TCR binding and T-cell recognition. These findings help to clarify the mechanism of T-cell recognition of gp100 during melanoma responses and could direct the development of altered peptides for vaccination.
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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.