{
  "abstract": "Celiac disease (CeD) is driven by pathogenic CD4 + T cell responses, primarily targeting four HLA-DQ2.5–restricted immunodominant epitopes derived from α-gliadin and ω-gliadin. While gliadin-specific CD4 + T cells have been investigated, how transcriptional and effector phenotypes in CeD vary across distinct epitope specificities remains unclear, as do the signature TCR motifs governing gliadin epitope specificity and cross-reactivity. Single-cell transcriptomic and TCR profiling of gliadin epitope-specific peripheral blood CD4 + T cells from patients with CeD after gluten challenge revealed T cells with an activated T H 1 effector, conventional regulatory T cell (T reg cell) or cytotoxic phenotypes across specificities, with no evidence of functional specialization driven by specific epitopes. Moreover, we identified core TCR motifs that dictate gliadin epitope specificity and cross-reactivity and elucidated the structural basis of their cognate pMHC recognition. These motifs enabled accurate prediction of gliadin specificity from unassigned TCRs. Collectively, these findings advance our understanding of immune responses in CeD and provide a foundation for tracking disease-relevant T cells.",
  "abstract_shown": true,
  "affiliations": [
    "Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.",
    "Department of Host-Microbe Interactions, St Jude Children’s Research Hospital, Memphis, TN, USA.",
    "Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.",
    "Janssen Research and Development, Spring House, PA, USA.",
    "Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia.",
    "Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.",
    "Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Claerwen M. Jones",
      "orcid": "0000-0001-8594-9554"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Jia Lim",
      "orcid": "0000-0002-6097-6238"
    },
    {
      "affs": [
        1
      ],
      "name": "Stefan A. Schattgen",
      "orcid": "0000-0002-6860-5079"
    },
    {
      "affs": [
        0
      ],
      "name": "Tiing Jen Loh",
      "orcid": "0000-0001-8470-6868"
    },
    {
      "affs": [
        0
      ],
      "name": "Hien Thy Dao",
      "orcid": "0009-0001-5492-0449"
    },
    {
      "affs": [
        0
      ],
      "name": "Mai T. Tran",
      "orcid": "0000-0001-6470-8663"
    },
    {
      "affs": [
        0
      ],
      "name": "Angela Nguyen",
      "orcid": "0000-0003-1610-515X"
    },
    {
      "affs": [
        2
      ],
      "name": "Pirooz Zareie",
      "orcid": "0000-0001-6000-2305"
    },
    {
      "affs": [
        3
      ],
      "name": "Nathan J. Felix"
    },
    {
      "affs": [
        1
      ],
      "name": "Paul G. Thomas",
      "orcid": "0000-0001-7955-0256"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Melinda Y. Hardy",
      "orcid": "0000-0003-4923-0678"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Jason A. Tye-Din",
      "orcid": "0000-0001-7687-9654"
    },
    {
      "affs": [
        0
      ],
      "name": "Hugh H. Reid",
      "orcid": "0000-0001-6929-5001"
    },
    {
      "affs": [
        0
      ],
      "name": "Jamie Rossjohn",
      "orcid": "0000-0002-2020-7522"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicole L. La Gruta",
      "orcid": "0000-0001-5358-9363"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/az4jeb14czpjt.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aei3175",
  "fulltext_url": null,
  "id": "az4jeb14czpjt",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aei3175",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2715|Celiac Disease Research and Management"
    ]
  ],
  "openalex": "W7216302261",
  "pdf_url": "https://www.science.org/doi/pdf/10.1126/sciadv.aei3175?download=true",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/az4jeb14czpjt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aei3175",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aei3175"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2715|Celiac Disease Research and Management",
      "subfield": "general"
    }
  ],
  "title": "Gliadin-specific CD4 ⁺ T cells exhibit functional diversity independent of TCR usage or epitope specificity",
  "title_text": "Gliadin-specific CD4 ⁺ T cells exhibit functional diversity independent of TCR usage or epitope specificity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/az4jeb14czpjt",
  "venue": "Science Advances",
  "versions": []
}