ArticleProceedings of the National Academy of Sciences of the United States of America2016
How structural adaptability exists alongside HLA-A2 bias in the human αβ TCR repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Decoding TCR recognition via geometric deep learning of immunological fingerprints.Briefings in bioinformatics · 2026Article
- Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes.iScience · 2025Article
- A pan-disease and population-level single-cell TCRαβ repertoire reference.Cell discovery · 2025Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- Broadening alloselectivity of T cell receptors by structure guided engineering.Scientific reports · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- Selection, engineering, and in vivo testing of a human leukocyte antigen-independent T-cell receptor recognizing human mesothelin.PloS one · 2024Article
- Article
- Computational Methods in Immunology and Vaccinology: Design and Development of Antibodies and Immunogens.Journal of chemical theory and computation · 2023Review
- Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities.Cell systems · 2023Article
- Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules.Frontiers in immunology · 2023Article
- A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry.Nature communications · 2022Article
- Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022Review
- Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma.Scientific reports · 2022Article
- Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules.PNAS nexus · 2022Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
- Computationally profiling peptide:MHC recognition by T-cell receptors and T-cell receptor-mimetic antibodies.Frontiers in immunology · 2022Article
- Tumor rejection properties of gp100Molecular immunology · 2021Article
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
How T-cell receptors (TCRs) can be intrinsically biased toward MHC proteins while simultaneously display the structural adaptability required to engage diverse ligands remains a controversial puzzle. We addressed this by examining αβ TCR sequences and structures for evidence of physicochemical compatibility with MHC proteins. We found that human TCRs are enriched in the capacity to engage a polymorphic, positively charged "hot-spot" region that is almost exclusive to the α1-helix of the common human class I MHC protein, HLA-A*0201 (HLA-A2). TCR binding necessitates hot-spot burial, yielding high energetic penalties that must be offset via complementary electrostatic interactions. Enrichment of negative charges in TCR binding loops, particularly the germ-line loops encoded by the TCR Vα and Vβ genes, provides this capacity and is correlated with restricted positioning of TCRs over HLA-A2. Notably, this enrichment is absent from antibody genes. The data suggest a built-in TCR compatibility with HLA-A2 that biases receptors toward, but does not compel, particular binding modes. Our findings provide an instructional example for how structurally pliant MHC biases can be encoded within TCRs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.