Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4TRAJ21-TRBV28TRBJ2-3 and TRAV4 TRAJ8-TRBV9TRBJ2-1), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-1. Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-1-HLA-B*07:02 complex, and induces differing extent of conformational change of the NY-ESO-1 epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847591 | PMC |
| http://dx.doi.org/10.1038/s41467-018-03321-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting mutated KRAS by HLA-A*02:01 restricted anti-KRAS TCR-mimic CAR and bispecific T cell engager.
J Mol Med (Berl)
August 2025
IIIrd. Department of Medicine - Hematology & Medical Oncology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Mutations in the KRAS proto-oncogene, particularly at codon 12, are among the most frequent genetic alterations in various cancers, and KRAS accounts for about 25% of all KRAS mutations observed in lung, pancreatic, and colorectal adenocarcinomas. Despite improved treatment regimes using targeted therapy and checkpoint inhibitors, cellular immunotherapy options for KRAS-mutated cancers remain elusive. We therefore developed two TCR-mimic (TCRm) anti-KRAS/HLA-A*02:01 chimeric antigen receptors (CARs) containing different hinge regions and, alternatively, a TCRm anti-KRAS/HLA-A*02:01 bispecific T cell engager (BiTE) to explore immunotherapy to the highly prevalent KRAS neoantigen.
View Article and Find Full Text PDFIlluminating cancer therapy via cryptic antigens.
Trends Cancer
July 2025
Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China. Electronic address:
A recent study in Science by Ely et al. identifies immunogenic, cancer-restricted noncanonical HLA-I-bound peptides (ncHLAp) in pancreatic cancer. Using a translation-informed filtering strategy, the study uncovers cryptic antigens derived from unannotated ORFs and validate antigen-specific T cell receptors (TCRs) capable of targeting pancreatic ductal adenocarcinoma (PDAC) in preclinical models, offering new avenues for immunotherapy.
View Article and Find Full Text PDFPopulation-level toggling of T cell immune escape at human leukocyte antigen anchor residues in SARS-CoV-2 Spike proteins, in an ethnically diverse population region.
PLoS Comput Biol
July 2025
South African National Bioinformatics Institute (SANBI), University of the Western Cape, Cape Town, South Africa.
There is currently limited understanding of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adaptation to the human leukocyte antigen (HLA) proteins which mediate CD8 (HLA-I) and CD4 (HLA-II) T cell immune responses. We investigated population-level T cell immune escape in SARS-CoV-2 Spike protein at amino acid binding positions (the anchor motifs) preferred by the highly restrictive peptide binding grooves of the HLA. SARS-CoV-2 Spike protein sequences isolated in South Africa from January 2020 until June 2022, were used.
View Article and Find Full Text PDFTherapeutic potential of T-cell receptor targeting the HLA-A*11:01-restricted KRAS neoantigen without cross-recognition of the self-antigen RAB7B in solid tumors.
J Immunother Cancer
July 2025
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Background: Public neoantigens, including KRAS, TP53, and PIK3CA mutations, which are shared across various tumor types, have demonstrated significant immunogenicity and offer great promise for cancer immunotherapy. Clinical trials targeting these public neoantigens have yielded encouraging results, including tumor regression and prolonged relapse-free survival. This study evaluates the human leukocyte antigen (HLA) binding properties of T-cell epitopes derived from these public neoantigens to identify optimal T-cell target and further develops T-cell receptor (TCR)-based therapeutics.
View Article and Find Full Text PDFMice with a diverse human T cell receptor repertoire selected on multiple HLA class I molecules.
Nat Commun
July 2025
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
T cell receptor (TCR) gene therapy is an effective cancer treatment. Ideally, the TCR should be of human origin and have optimal avidity, e.g.
View Article and Find Full Text PDF