{
  "abstract": "Peripheral differentiation of regulatory T (pTreg) cells promotes immunological tolerance to obligate non-self, such as food or symbiotic microbes. We examined the relative importance of TCR recognition vs. environmental cues, leveraging CRISPR-based TCR editing of primary T cells with a large TCR panel, assessing pTreg cell differentiation induced by self-, microbial, or dietary antigens. All antigen classes drove stable pTreg cell differentiation, which varied with TCR origin: TCRs derived from Treg cells enabled pTreg cell differentiation more effectively than those from conventional T cells. TCRs recognizing self-, microbial, or dietary antigens elicited distinct pTreg cell phenotypes: Helios⁺, RORγ⁺, or both. Different TCR-antigen pairs established distinct transcriptional programs. These differences traced to the types of antigen-presenting cells (APCs) involved—food-reactive TCRs depended predominantly on RORγ⁺ APCs and self-reactive TCRs depended on conventional dendritic cells. Thus, TCR specificity is a primary determinant of CD4 + T cell fate and phenotype, integrating antigen specificity and presentation context, providing a framework to design TCR-based tolerogenic immunotherapies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, Harvard Medical School, Boston, MA, USA",
    "Department of Medicine, University of California, San Francisco, San Francisco, CA, USA",
    "Immuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Immuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Immuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine Graduate School of Medical Sciences, New York, NY, USA",
    "Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address: cbdm@hms.harvard.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinxin Chi",
      "orcid": "0000-0003-2120-6684"
    },
    {
      "affs": [
        1
      ],
      "name": "Charlotte H. Wang",
      "orcid": "0000-0001-7588-2077"
    },
    {
      "affs": [
        2
      ],
      "name": "Yollanda Franco Parisotto"
    },
    {
      "affs": [
        1
      ],
      "name": "William A. Nyberg",
      "orcid": "0000-0002-9982-1305"
    },
    {
      "affs": [
        3
      ],
      "name": "Vanja Cabric",
      "orcid": "0009-0004-8941-2083"
    },
    {
      "affs": [
        0
      ],
      "name": "Adélaïde Gélineau",
      "orcid": "0000-0002-5140-7981"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Cao",
      "orcid": "0000-0002-1279-5491"
    },
    {
      "affs": [
        0
      ],
      "name": "David L. Owen",
      "orcid": "0000-0002-1099-0605"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonas Ambjörnsson",
      "orcid": "0009-0000-1569-2351"
    },
    {
      "affs": [
        0
      ],
      "name": "Diane J. Mathis",
      "orcid": "0000-0002-6110-4626"
    },
    {
      "affs": [
        1
      ],
      "name": "Justin Eyquem",
      "orcid": "0000-0001-8262-1190"
    },
    {
      "affs": [
        4
      ],
      "name": "Chrysothemis C. Brown",
      "orcid": "0000-0002-5834-926X"
    },
    {
      "affs": [
        5
      ],
      "name": "Christophe O. Benoist",
      "orcid": "0000-0003-1172-6555"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/699r4k3z4bk9d.bib",
  "cited_by": 6,
  "doi": "10.1016/j.immuni.2026.07.001",
  "fulltext_url": null,
  "id": "699r4k3z4bk9d",
  "issns": [
    "1074-7613",
    "1097-4180"
  ],
  "landing_url": "https://doi.org/10.1016/j.immuni.2026.07.001",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7171526642",
  "pdf_url": null,
  "pmcid": "PMC12633282",
  "pmid": "41279359",
  "published": "2026-07-28",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/699r4k3z4bk9d.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:10Z",
      "native_id": "W7171526642",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.immuni.2026.07.001"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "TCR origin and specificity to environmental or self-antigens on distinct antigen-presenting cells determine peripheral Treg cell differentiation",
  "title_text": "TCR origin and specificity to environmental or self-antigens on distinct antigen-presenting cells determine peripheral Treg cell differentiation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/699r4k3z4bk9d",
  "venue": "Immunity",
  "versions": []
}