Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of T <sub>H</sub> 1-like γδT cells
Of the three classes of lymphocytes that constitute the adaptive immune system, γδT cells are the only class for which the principles of antigen recognition remain enigmatic. Although endogenous γδT cell antigen receptor (γδTCR) ligands are thought to regulate γδT cell development, their identities are largely elusive. Here, we identified the interleukin 17 receptor A chain (IL17RA) as a γδTCR ligand that drove the differentiation of Vδ7 + γδT cells with a T helper 1 (T H 1)–like effector program in mice. IL17RA promoted this differentiation through an interaction involving germline-encoded regions of the Vδ7 chain, enabling the selection of cells with a diverse CDR3 repertoire and thus acting as a nonclonotypic γδTCR ligand. Together with the nonclonotypic mode of γδTCR engagement by butyrophilins, these results suggest that such interactions represent a general biological mechanism shaping the γδT cell compartment.
Authors
- Erik Benson (ORCID: https://orcid.org/0000-0003-3374-501X)
- Ken‐ichi Hanada (ORCID: https://orcid.org/0000-0003-2959-1257)
- Iris Rocamonde-Lago (ORCID: https://orcid.org/0000-0002-6923-5313)
- Kewei Ye
- Tomás J. Ryan (ORCID: https://orcid.org/0000-0003-0121-8514)
- Anatoly Dubnovitsky (ORCID: https://orcid.org/0000-0002-5350-4531)
- Tommy Regen (ORCID: https://orcid.org/0000-0002-7275-3330)
- Ari Waisman (ORCID: https://orcid.org/0000-0003-4304-8234)
- Jan Kisielow (ORCID: https://orcid.org/0000-0002-4482-5202)
- Taras Kreslavsky (ORCID: https://orcid.org/0000-0002-6672-1914)
- Thomas Krey (ORCID: https://orcid.org/0000-0002-4548-7241)
- Josefine Dunst (ORCID: https://orcid.org/0000-0003-0061-0901)
- Stefanie Köhler (ORCID: https://orcid.org/0000-0002-7417-333X)
- Leo Hanke (ORCID: https://orcid.org/0000-0001-5514-2418)
- Vivianne Malmström (ORCID: https://orcid.org/0000-0001-9251-8082)
- Thomas Winkler (ORCID: https://orcid.org/0000-0002-1860-0528)
- Yuanyuan You (ORCID: https://orcid.org/0000-0002-6047-2742)
- Valentin Zollner
- Fanxi Meng
- Lisa Vogg (ORCID: https://orcid.org/0009-0003-8118-0620)
- Amanda Borgenstam
- Anja Kramer
- Nimmy Francis (ORCID: https://orcid.org/0000-0003-2650-5413)
Institutions
- Canadian Institute for Advanced Research (CA)
- National Institutes of Health (US)
- Karolinska University Hospital (SE)
- The University of Melbourne (AU)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Johannes Gutenberg University Mainz (DE)
- Trinity College Dublin (IE)
- Florey Institute of Neuroscience and Mental Health (AU)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Medizinische Hochschule Hannover (DE)
- University of Chicago (US)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- German Center for Infection Research (DE)
- National Cancer Institute (US)
- Centre for Structural Systems Biology (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Science
- Published
- 2026-07-16
- DOI
- https://doi.org/10.1126/science.adx9264
- Primary Topic
- Psoriasis: Treatment and Pathogenesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Hypothesis Fund
- Deutsche Forschungsgemeinschaft
- Cancerfonden
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Barncancerfonden
- Radiumhemmets Forskningsfonder