ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
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- Immuno-informatics voyage through molecular mimicry of Heat Shock Proteins: Potential IBD immunopathogenesis.PloS one · 2025Article
- Machine learning application to predict binding affinity between peptide containing non-canonical amino acids and HLA-A0201.PloS one · 2025Article
- Experimental Data on PIRCHE and T-Cell Reactivity: HLA-DPB1-Derived Peptides Identified by PIRCHE-I Show Binding to HLA-A*02:01 in vitro and T-Cell Activation in vivo.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2024Article
- Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens.Current oncology (Toronto, Ont.) · 2024Article
- An Efficient Approach to the Accurate Prediction of Mutational Effects in Antigen Binding to the MHC1.Molecules (Basel, Switzerland) · 2024Article
- Structural and Dynamic-Based Characterization of the Recognition Patterns of E7 and TRP-2 Epitopes by MHC Class I Receptors through Computational Approaches.International journal of molecular sciences · 2024Article
- Modified influenza M1NPJ vaccines · 2023Article
- Analysis of protonation equilibria of some alanyl dipeptides in water and aqueous ethanol mixtures.Amino acids · 2023Article
- Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules.Frontiers in immunology · 2023Article
- EnhancedJournal of virology · 2022Article
- Electrostatically induced pKAmino acids · 2022Article
- Structural aspects of chemical modifications in the MHC-restricted immunopeptidome; Implications for immune recognition.Frontiers in chemistry · 2022Review
- Enhancing Antigen Presentation and Inducing Antigen-Specific Immune Tolerance with Amphiphilic Peptides.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Nucleic Acid-Based Approaches for Tumor Therapy.Cells · 2020Review
- MHC Class I Stability is Modulated by Cell Surface Sialylation in Human Dendritic Cells.Pharmaceutics · 2020Article
- Peptide mimotopes alter T cell function in cancer and autoimmunity.Seminars in immunology · 2020Review
- DNA Vaccines-How Far From Clinical Use?International journal of molecular sciences · 2018Review
- Article
- A modified HLA-A*0201-restricted CTL epitope from human oncoprotein (hPEBP4) induces more efficient antitumor responses.Cellular & molecular immunology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Virus or tumor Ag-derived peptides that are displayed by MHC class I molecules are attractive starting points for vaccine development because they induce strong protective and therapeutic cytotoxic T cell responses. In thus study, we show that the MHC binding and consequent T cell reactivity against several HLA-A*02 restricted epitopes can be further improved through the incorporation of nonproteogenic amino acids at primary and secondary anchor positions. We screened more than 90 nonproteogenic, synthetic amino acids through a range of epitopes and tested more than 3000 chemically enhanced altered peptide ligands (CPLs) for binding affinity to HLA-A*0201. With this approach, we designed CPLs of viral epitopes, of melanoma-associated Ags, and of the minor histocompatibility Ag UTA2-1, which is currently being evaluated for its antileukemic activity in clinical dendritic cell vaccination trials. The crystal structure of one of the CPLs in complex with HLA-A*0201 revealed the molecular interactions likely responsible for improved binding. The best CPLs displayed enhanced affinity for MHC, increasing MHC stability and prolonging recognition by Ag-specific T cells and, most importantly, they induced accelerated expansion of antitumor T cell frequencies in vitro and in vivo as compared with the native epitope. Eventually, we were able to construct a toolbox of preferred nonproteogenic residues with which practically any given HLA-A*02 restricted epitope can be readily optimized. These CPLs could improve the therapeutic outcome of vaccination strategies or can be used for ex vivo enrichment and faster expansion of Ag-specific T cells for transfer into patients.
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