{
  "abstract": "The T cell receptor (TCR) repertoire enables recognition of a vast array of pathogens, despite containing far fewer unique TCRs than the diversity of encountered epitopes. This potential contradiction is resolved by TCR cross-reactivity, whereby individual TCRs recognize multiple distinct epitopes. However, the features defining broadly cross-reactive TCRs remain poorly understood. Here we systematically analyze TCRs from mice sequentially infected with influenza viruses containing naturally occurring single amino acid variants of the D b NP 366 epitope. We identify 967 unique paired TCR sequences across 18 infection histories and test 22 representative TCRs against 172 epitope variants, yielding 3,784 TCR-epitope interaction measurements. These TCRs exhibit a continuum of cross-reactivity, with infection history influencing both TCR sequence similarity and reactivity profiles. We find specific TCR sequence features associated with broader cross-reactivity, highlighting the interplay between epitope exposure, TCR diversity, and function, and providing insights into CD8 + T cell adaptability, immune memory, and vaccine design.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "Jessica A. Gaevert",
      "orcid": "0000-0002-4043-2161"
    },
    {
      "name": "Koshlan Mayer-Blackwell",
      "orcid": "0000-0002-1652-4023"
    },
    {
      "name": "Mikhail V. Pogorelyy"
    },
    {
      "name": "Stefan A. Schattgen"
    },
    {
      "name": "Allison M. Kirk",
      "orcid": "0000-0002-4286-3678"
    },
    {
      "name": "Susu Duan"
    },
    {
      "name": "Lee-Ann Van de Velde",
      "orcid": "0009-0000-6205-1151"
    },
    {
      "name": "Aisha Hegab Souquette",
      "orcid": "0000-0001-6197-5870"
    },
    {
      "name": "Walid Awad"
    },
    {
      "name": "Deryn G. St. James",
      "orcid": "0009-0002-7410-5588"
    },
    {
      "name": "Nicholas A. Clark"
    },
    {
      "name": "Daniel Luque Duque",
      "orcid": "0000-0002-4404-8749"
    },
    {
      "name": "E. Kaitlynn Allen",
      "orcid": "0000-0002-3067-751X"
    },
    {
      "name": "Grant Lythe"
    },
    {
      "name": "Carmen Molina-Paris"
    },
    {
      "name": "Jeremy Chase Crawford"
    },
    {
      "name": "Andrew Fiore-Gartland",
      "orcid": "0000-0001-7627-2166"
    },
    {
      "name": "Philip Bradley",
      "orcid": "0000-0002-0224-6464"
    },
    {
      "name": "Anastasia A. Minervina"
    },
    {
      "name": "Paul G. Thomas",
      "orcid": "0000-0001-7955-0256"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/92sjyt8yb9bsw.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.118182",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2211124726012611",
  "id": "92sjyt8yb9bsw",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726012611",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7223469071",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/92sjyt8yb9bsw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:34Z",
      "native_id": "10.1016/j.celrep.2026.118182",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726012611"
    },
    {
      "first_seen": "2026-10-30T13:44:57Z",
      "native_id": "a3d052c6584b4e078c3097f9d746daf8",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.celrep.2026.118182"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Infection history and TCR sequence features shape the breadth of TCR cross-reactivity",
  "title_text": "Infection history and TCR sequence features shape the breadth of TCR cross-reactivity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:57Z",
  "url": "https://research.draconitic.com/paper/92sjyt8yb9bsw",
  "venue": "Cell Reports",
  "versions": []
}