{
  "abstract": "Intestinal V{gamma}4 {gamma}{delta} intraepithelial lymphocytes (IELs) persistently bind the constitutively expressed epithelial ligand BTNL3/8 through germline-encoded T cell receptor (TCR) determinants. While they resemble innate-like T cells such as NKT cells, unlike these populations, V{gamma}4 IELs encounter ligand only after thymic development. Moreover, unlike conventional {beta} T cells, V{gamma}4 IELs sustain persistent physiological ligand engagement without becoming exhausted. Here, using biophysical, functional, and multimodal single-cell approaches, we show how V{gamma}4 IELs address this challenge. While germline-encoded TCR regions broadly mediate BTNL3 recognition, productive activation requires additional non-germline TCR features that license responsiveness to BTNL3/8 and enable local selection in the gut. Rather than driving exhaustion, BTNL3/8 reactivity directly promotes expression of an NK-like program marked by adaptor molecules that license innate-like signaling in healthy tissue. These findings reveal how combined innate and adaptive features of the {gamma}{delta}TCR enable durable tissue specialization under conditions of persistent physiological ligand engagement.",
  "abstract_shown": true,
  "affiliations": [
    "Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "B. D. McDonald"
    },
    {
      "name": "H. D. Anderson"
    },
    {
      "name": "T. Mayassi"
    },
    {
      "name": "C. L. Sok"
    },
    {
      "name": "V. Locher"
    },
    {
      "name": "M. Justyniarska"
    },
    {
      "name": "M. E. Borregard"
    },
    {
      "name": "C. Kaiser"
    },
    {
      "name": "K. Ladell"
    },
    {
      "name": "J. E. McLaren"
    },
    {
      "name": "D. A. Price"
    },
    {
      "name": "N. Hibino"
    },
    {
      "name": "A. S. Koh"
    },
    {
      "name": "J. Rossjohn"
    },
    {
      "name": "B. S. Gully"
    },
    {
      "affs": [
        0
      ],
      "name": "S. J. Riesenfeld"
    },
    {
      "name": "B. Jabri"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/07rckk752pq3d.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.751481",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.751481v1.full",
  "id": "07rckk752pq3d",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.751481v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7214206382",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.751481v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/07rckk752pq3d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:22Z",
      "native_id": "10.64898/2026.09.17.751481",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.751481v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Adaptive-like features of the γδ TCR couple chronic BTNL recognition to NK-like tissue immunity",
  "title_text": "Adaptive-like features of the γδ TCR couple chronic BTNL recognition to NK-like tissue immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:22Z",
  "url": "https://research.draconitic.com/paper/07rckk752pq3d",
  "venue": "bioRxiv",
  "versions": []
}