{
  "abstract": "Public T cell receptors (TCRs) recurrently emerge across individuals in response to common pathogens, yet the structural and biophysical basis distinguishing public from private clonotypes remains incompletely defined. Here, we combine epitope mapping, single-cell TCR sequencing, and single-particle cryo-electron microscopy to dissect CD8⁺ T cell responses to the immunodominant SARS-CoV-2 ORF3a₍₂₀₇₋₂₁₅₎ epitope presented by HLA-A*01:01. Among responding clonotypes, we identify a public TCR (TCRpub), shared across donors, and a private TCR (TCRpriv) that uses nearly identical β chains but distinct α chains. Despite comparable micromolar affinities and functional avidities, cryo-EM structures at ~3 Å resolution reveal that the two receptors engage the peptide-MHC complex through distinct CDR-loop configurations and contact footprints. TCRpub establishes contacts with the peptide and the MHC α2-helix primarily through the CDR2β and CDR3β loops, whereas TCRpriv distributes contacts across both MHC α-helices and engages the peptide via multiple CDR loops. In agreement with these observations, alanine-scanning mutagenesis reveals that TCRpub shows greater sensitivity to peptide substitutions, consistent with its peptide-focused binding mode. These findings demonstrate how alternative α-chain pairing reconfigures the antigen-binding interface within a shared β-chain.",
  "abstract_shown": true,
  "affiliations": [
    "Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.",
    "Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.",
    "MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.",
    "Institute for Advanced Study in Physics, Zhejiang University, Hangzhou, Zhejiang, China.",
    "Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.",
    "Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. ricardo.fernandes@ndm.ox.ac.uk.",
    "Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. tao.dong@ndm.ox.ac.uk.",
    "MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. tao.dong@ndm.ox.ac.uk.",
    "Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. peijun.zhang@strubi.ox.ac.uk.",
    "Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, UK. peijun.zhang@strubi.ox.ac.uk.",
    "Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK. peijun.zhang@strubi.ox.ac.uk."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Caner Akıl",
      "orcid": "0000-0002-9464-1903"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yanchun Peng",
      "orcid": "0000-0003-2340-0499"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia McCarthy"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Yanan Zhu",
      "orcid": "0000-0003-1025-7929"
    },
    {
      "affs": [
        1
      ],
      "name": "Nathan Hardenbrook"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunkai Yang",
      "orcid": "0000-0002-2240-807X"
    },
    {
      "affs": [
        0
      ],
      "name": "Danning Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Elie Antoun",
      "orcid": "0000-0002-9477-1564"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuan Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Guihai Liu",
      "orcid": "0009-0003-3684-4870"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ji-Li Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Esra Balıkçı",
      "orcid": "0009-0000-9160-5790"
    },
    {
      "affs": [
        0
      ],
      "name": "Raul Cioaca"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Alexander J Mentzer",
      "orcid": "0000-0002-4502-2209"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Julian C Knight",
      "orcid": "0000-0002-0377-5536"
    },
    {
      "affs": [
        5
      ],
      "name": "Ricardo A Fernandes",
      "orcid": "0000-0001-5343-3334"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Tao Dong",
      "orcid": "0000-0003-3545-3758"
    },
    {
      "affs": [
        8,
        9,
        10
      ],
      "name": "Peijun Zhang",
      "orcid": "0000-0003-1803-691X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e19tybvajjkrs.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77827-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13687542",
  "id": "e19tybvajjkrs",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907447",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7214002191",
  "pdf_url": "https://europepmc.org/articles/PMC13687542?pdf=render",
  "pmcid": "PMC13687542",
  "pmid": "42907447",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e19tybvajjkrs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907447",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907447"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Unveiling structural determinants of peptide recognition by public and private SARS-CoV-2-specific T-cell receptors.",
  "title_text": "Unveiling structural determinants of peptide recognition by public and private SARS-CoV-2-specific T-cell receptors.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/e19tybvajjkrs",
  "venue": "Nature communications",
  "versions": []
}