ArticleThe Journal of biological chemistry2012
T-cell receptor-optimized peptide skewing of the T-cell repertoire can enhance antigen targeting.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Tumor cell spheroid-induced suppression of primary human cytotoxic T cells as a scalableImmunotherapy advances · 2025Article
- Thioamide Analogues of MHC I Antigen Peptides.Journal of the American Chemical Society · 2023Article
- Modified influenza M1NPJ vaccines · 2023Article
- Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes.Frontiers in immunology · 2023Article
- Seeing the T cell Immunity of SARS-CoV-2 and SARS-CoV: Believing the Epitope-Oriented Vaccines.International journal of biological sciences · 2023Review
- Synthetic Peptides with Inadvertent Chemical Modifications Can Activate Potentially Autoreactive T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- Backbone Modifications of HLA-A2-Restricted Antigens Induce Diverse Binding and T Cell Activation Outcomes.Journal of the American Chemical Society · 2021Article
- Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors.Frontiers in immunology · 2020Review
- T-cell Receptors EngineeredCancer immunology research · 2019Article
- Rapid selection and identification of functional CD8Nature communications · 2019Article
- T-cell-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation.Immuno-oncology technology · 2019Review
- TCR-induced alteration of primary MHC peptide anchor residue.European journal of immunology · 2019Article
- Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Peptide Super-Agonist Enhances T-Cell Responses to Melanoma.Frontiers in immunology · 2019Article
- The expanding role of systems immunology in decoding the T cell receptor repertoire.Current opinion in systems biology · 2018Article
- Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry.The Journal of clinical investigation · 2018Article
- Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens.Journal of visualized experiments : JoVE · 2017Article
- Using Global Analysis to Extend the Accuracy and Precision of Binding Measurements with T cell Receptors and Their Peptide/MHC Ligands.Frontiers in molecular biosciences · 2017Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Altered peptide antigens that enhance T-cell immunogenicity have been used to improve peptide-based vaccination for a range of diseases. Although this strategy can prime T-cell responses of greater magnitude, the efficacy of constituent T-cell clonotypes within the primed population can be poor. To overcome this limitation, we isolated a CD8(+) T-cell clone (MEL5) with an enhanced ability to recognize the HLA A*0201-Melan A(27-35) (HLA A*0201-AAGIGILTV) antigen expressed on the surface of malignant melanoma cells. We used combinatorial peptide library screening to design an optimal peptide sequence that enhanced functional activation of the MEL5 clone, but not other CD8(+) T-cell clones that recognized HLA A*0201-AAGIGILTV poorly. Structural analysis revealed the potential for new contacts between the MEL5 T-cell receptor and the optimized peptide. Furthermore, the optimized peptide was able to prime CD8(+) T-cell populations in peripheral blood mononuclear cell isolates from multiple HLA A*0201(+) individuals that were capable of efficient HLA A*0201(+) melanoma cell destruction. This proof-of-concept study demonstrates that it is possible to design altered peptide antigens for the selection of superior T-cell clonotypes with enhanced antigen recognition properties.
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