{
  "abstract": "The gamma delta T-cell receptor ({gamma}{delta} TCR) mediates {gamma}{delta} T-cell responses that are crucial for immune defense, tissue surveillance, and homeostasis. While recent studies suggest that {gamma}{delta} TCRs engage ligands multivalently, how multivalent engagement activates the {gamma}{delta} TCR remains elusive. Here, we present the structures of the V{gamma}9V{delta}2 (clone G115) TCR in both the inactive and the agonist-crosslinked active states. In the {gamma}{delta} TCR lipoprotein complex, cholesterol and phospholipids form a \"barrier\" that isolates CD3{zeta}{zeta} from the other subunits and likely prevents autoactivation. As an agonist, the Fab fragment of the UCHT1 antibody dimerizes upon binding the V{gamma}9V{delta}2 TCR, thereby crosslinking and activating the receptor. Cryo-EM analysis of Fab-crosslinked V{gamma}9V{delta}2 TCR identifies three Fab dimer interfaces, one between the two light chains and the other two between light and heavy chains. These Fab-Fab interfaces, together with the Fab-CD3{epsilon} interface, mediate the assembly of the V{gamma}9V{delta}2 TCR and UCHT1 Fab into 2:2 tetramers. Upon activation, the V{gamma}9V{delta}2 TCR becomes conformationally plastic and loses enriched lipids, including cholesterol and phosphatidylethanolamine. Our findings reveal a dimerization-driven activation mechanism, inform the design of rigid TCR-crosslinking agonists, and suggest multivalency-induced clustering as a general paradigm for {gamma}{delta} TCR activation.",
  "abstract_shown": true,
  "affiliations": [
    "Wuhan University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Z. Li"
    },
    {
      "name": "Y. Fan"
    },
    {
      "name": "J. Li"
    },
    {
      "name": "Y. Zhao"
    },
    {
      "name": "L. Chen"
    },
    {
      "name": "Y. Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Z. Wang"
    },
    {
      "name": "Y. Zheng"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Wang"
    },
    {
      "name": "H. Wu"
    },
    {
      "name": "D. Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b5wmr2xhccsg6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757522",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757522v1.full",
  "id": "b5wmr2xhccsg6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757522v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7221943162",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757522v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b5wmr2xhccsg6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:59Z",
      "native_id": "10.64898/2026.10.08.757522",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757522v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Structural Basis of γδ T-Cell Receptor Crosslinking and Activation by a Spontaneously Dimerized Fab",
  "title_text": "Structural Basis of γδ T-Cell Receptor Crosslinking and Activation by a Spontaneously Dimerized Fab",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:10Z",
  "url": "https://research.draconitic.com/paper/b5wmr2xhccsg6",
  "venue": "bioRxiv",
  "versions": []
}