ArticleThe Journal of experimental medicine2001
Structural features of peptide analogs of human histocompatibility leukocyte antigen class I epitopes that are more potent and immunogenic than wild-type peptide.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 145 citations in OpenAlex.
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- Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.Cancer immunology, immunotherapy : CII · 2013Trial
- Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma.Blood · 2007Trial
- Distinguishing Ile/Leu Variant Ligands in the Immunopeptidome Using Hybrid EAD + CID Fragmentation (ExCID).Analytical chemistry · 2026Article
- A Reproducible Sequence-Level Strategy to Enhance Peptide Immunogenicity While Preserving Wild-Type Epitope Recognition.Antibodies (Basel, Switzerland) · 2025Article
- Isolation and characterization ofSaudi journal of biological sciences · 2023Article
- Thioamide Analogues of MHC I Antigen Peptides.Journal of the American Chemical Society · 2023Article
- EnhancedJournal of virology · 2022Article
- A Systematic Review of T Cell Epitopes Defined from the Proteome of Hepatitis B Virus.Vaccines · 2022Review
- Identification of an immunogenic DKK1 long peptide for immunotherapy of human multiple myeloma.Haematologica · 2021Article
- Immunogenicity of Calvenza-03 EIV/EHVVaccines · 2021Article
- Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting.Cell reports. Medicine · 2021Article
- Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes.Biomolecules · 2016Article
- Expressing Redundancy among Linear-Epitope Sequence Data Based on Residue-Level Physicochemical Similarity in the Context of Antigenic Cross-Reaction.Advances in bioinformatics · 2016Article
- Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma.Bone marrow transplantation · 2015Review
- Enhancing Human Immunodeficiency Virus-Specific CD8(+) T Cell Responses with Heteroclitic Peptides.Frontiers in immunology · 2015Review
- Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Human heat shock protein-specific cytotoxic T lymphocytes display potent antitumour immunity in multiple myeloma.British journal of haematology · 2014Article
- An unstable Th epitope of P. falciparum fosters central memory T cells and anti-CS antibody responses.PloS one · 2014Article
- Accurate structure prediction of peptide-MHC complexes for identifying highly immunogenic antigens.Molecular immunology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Certain peptide analogs that carry substitutions at residues other than the main major histocompatibility complex anchors and are surprisingly much more antigenic than wild-type peptide (heteroclitic analogs). To date, it was unknown how frequently wild-type epitopes could be modified to obtain heteroclitic activity. In this study, we analyzed a large panel of analogs of two different human histocompatibility leukocyte antigen (HLA)-A2.1-restricted epitopes and found that heteroclitic analogs were associated with higher magnitude responses and increased (up to 10(7)-fold) sensitivity to antigen, and corresponded to conservative or semiconservative substitutions at odd-numbered positions in the middle of the peptide (positions 3, 5, or 7). These findings were validated by performing additional immunogenicity studies in murine and human systems with four additional epitopes. The biological relevance of heteroclitic analogs was underlined when predicted analogs of the p53.261 epitope was shown to induce cytotoxic T lymphocytes (CTLs) that recognize low concentrations of peptide (high avidity) in vivo and demonstrate in vitro antitumor recognition. Finally, in vitro immunization of human peripheral blood mononuclear cells with two heteroclitic analogs resulted in recruitment of more numerous CTLs which were associated with increased antigen sensitivity. In conclusion, heteroclitic analogs were identified in each of the six cases studied and structural features were defined which allow identification of such analogs. The strong CTL immunity elicited by heteroclitic epitopes suggest that they could be of significant value in vaccination against tolerant or weakly immunogenic tumor-associated and viral antigens.
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