ArticleThe Journal of biological chemistry2020
T cell receptor interactions with human leukocyte antigen govern indirect peptide selectivity for the cancer testis antigen MAGE-A4.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity.Scientific reports · 2022Pooled it
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- Computational identification of cross-reactive TCR epitopes with ARDitox.Journal of cancer research and clinical oncology · 2025Article
- Broadening alloselectivity of T cell receptors by structure guided engineering.Scientific reports · 2024Article
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- Memory T Cells in the Immunoprevention of Cancer: A Switch from Therapeutic to Prophylactic Approaches.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Computational Methods in Immunology and Vaccinology: Design and Development of Antibodies and Immunogens.Journal of chemical theory and computation · 2023Review
- Epigenetic Factors and ncRNAs in Testicular Cancer.International journal of molecular sciences · 2023Review
- Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.Nature communications · 2023Article
- Therapeutic high affinity T cell receptor targeting a KRASNature communications · 2022Article
- Structural insights into engineering a T-cell receptor targeting MAGE-A10 with higher affinity and specificity for cancer immunotherapy.Journal for immunotherapy of cancer · 2022Article
- TCR mimic compounds for pHLA targeting with high potency modalities in oncology.Frontiers in oncology · 2022Review
- Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.Discovery immunology · 2022Review
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29.Frontiers in immunology · 2021Article
- TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers.International journal of molecular sciences · 2020Review
- HLA-A29 and Birdshot Uveitis: Further Down the Rabbit Hole.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell-mediated immunity is governed primarily by T cell receptor (TCR) recognition of peptide-human leukocyte antigen (pHLA) complexes and is essential for immunosurveillance and disease control. This interaction is generally stabilized by interactions between the HLA surface and TCR germline-encoded complementarity-determining region (CDR) loops 1 and 2, whereas peptide selectivity is guided by direct interactions with the TCR CDR3 loops. Here, we solved the structure of a newly identified TCR in complex with a clinically relevant peptide derived from the cancer testis antigen melanoma antigen-A4 (MAGE-A4). The TCR bound pHLA in a position shifted toward the peptide's N terminus. This enabled the TCR to achieve peptide selectivity via an indirect mechanism, whereby the TCR sensed the first residue of the peptide through HLA residue Trp-167, which acted as a tunable gateway. Amino acid substitutions at peptide position 1 predicted to alter the HLA Trp-167 side-chain conformation abrogated TCR binding, indicating that this indirect binding mechanism is essential for peptide recognition. These findings extend our understanding of the molecular rules that underpin antigen recognition by TCRs and have important implications for the development of TCR-based therapies.
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