γδ T cell receptor dependencies define a unique immunosurveillance modality
Abstract γδ T cells are one of three lymphocyte lineages that utilize gene rearrangement to diversify their antigen receptors. Nonetheless, the cells’ classification has remained uncertain, complicating our ability to understand the basis for their evolutionary conservation. Whereas many γδ T cells display hallmarks of adaptive immunity, others, including those in barrier tissues, make rapid, reportedly T cell receptor-independent responses that phenocopy innate immune cells 1 . Here we address this paradox and show that the phenotypes of tissue-intrinsic γδ T cells, including their rapid, innate-like responsiveness to tissue stress and carcinogenesis, acutely depend on the γδ T cell receptor (TCRγδ). Those dependencies emphasize the unique biology of γδ T cells and of the immunosurveillance modalities they mediate, with their clinical deployment evidently requiring environments conducive to TCRγδ signalling.
Authors
- Jessica Strid (ORCID: https://orcid.org/0000-0003-3690-2201)
- Miguel Muñoz‐Ruiz (ORCID: https://orcid.org/0000-0001-7986-3527)
- Ana V. Marín (ORCID: https://orcid.org/0000-0002-7541-3729)
- Ambra Natalini (ORCID: https://orcid.org/0000-0002-7618-493X)
- Bethania García-Cassani (ORCID: https://orcid.org/0000-0002-1315-133X)
- Anett Jandke (ORCID: https://orcid.org/0000-0002-7681-7952)
- Nicolás Veland (ORCID: https://orcid.org/0000-0002-3096-7867)
- John Franken (ORCID: https://orcid.org/0009-0006-2460-2841)
- Alejandro Suárez‐Bonnet (ORCID: https://orcid.org/0000-0003-0296-5896)
- Pierre Vantourout (ORCID: https://orcid.org/0000-0001-7287-5517)
- Duncan R. McKenzie (ORCID: https://orcid.org/0000-0003-0961-8846)
- Adrian Hayday (ORCID: https://orcid.org/0000-0002-9495-5793)
- Rosa Andres Ejarque (ORCID: https://orcid.org/0000-0003-0012-1155)
- Ángela Zarco-Cuadrillero (ORCID: https://orcid.org/0009-0001-1511-9624)
- Josephine Eum
- Annamaria Mavrigiannaki
Institutions
- Universidad Complutense de Madrid (ES)
- Royal Veterinary College (GB)
- King's College London (GB)
- University of Basel (CH)
- The Francis Crick Institute (GB)
- Research Institute Hospital 12 de Octubre (ES)
- London Cancer (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Centre for Inflammation Research (GB)
- Imperial College London (GB)
Publication Details
- Journal
- Nature
- Published
- 2026-09-30
- DOI
- https://doi.org/10.1038/s41586-026-11076-4
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00