ArticleProceedings of the National Academy of Sciences of the United States of America2015
TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07686744 (A Phase I Clinical Trial of Personalized Neoantigen Peptide Vaccine in Combination With Pembrolizumab for the Safety and Efficacy in Patients With Advanced, Recurrent or Refractory Renal Cell Carcinoma), which is not on this map. Cited by 158 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Phase I Clinical Trial of Personalized Neoantigen Peptide Vaccine in Combination With Pembrolizumab for the Safety and Efficacy in Patients With Advanced, Recurrent or Refractory Renal Cell Carcinoma
Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Cross-task interpretability through unified modeling reveals a universal shortcut bias in neoantigen prediction.Cell genomics · 2026Article
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- Five dominant amino acid substitution signatures shape tumour immunity.Molecular systems biology · 2026Article
- Identification of MHC Ligands Through Allele-Guided Isolation Combined With Machine Learning for Improved MHC Assignment Using ARDisplay-I.Molecular & cellular proteomics : MCP · 2026Article
- Advances in predicting T cell epitope recognition for cancer immunotherapy.Nature cancer · 2026Review
- Clinical development of cancer vaccines.Nature medicine · 2026Review
- The GF-NEO discovery platform unveils a [KQE][DG] sequence motif within fusion neoantigens in pediatric cancer.iScience · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- PredIG: an interpretable predictor of T-cell epitope immunogenicity.Genome medicine · 2025Article
- A machine learning-based method to optimize the immunogenicity of human leukocyte antigen class I-restricted neoantigens.Briefings in bioinformatics · 2025Article
- Structural changes from wild-type define tumor-rejecting neoantigens.Journal for immunotherapy of cancer · 2025Article
- T cell receptor cross-reactivity prediction improved by a comprehensive mutational scan database.Cell systems · 2025Article
- Accelerating Neoantigen Discovery: A High-Throughput Approach to Immunogenic Target Identification.Vaccines · 2025Article
- Site-directed multivalent conjugation of antibodies to ubiquitinated payloads.Nature biomedical engineering · 2025Article
- Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation.Nature biotechnology · 2025Article
- A frameshift-generated cancer neoepitope that controls tumor burden in prophylaxis as well as therapy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Engineering a New Generation of Gene Editors: Integrating Synthetic Biology and AI Innovations.ACS synthetic biology · 2025Review
98 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8(+) T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.
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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.