Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of TH1-like γδT cells

Ye K, Francis N, Dunst J, Borgenstam A, Rocamonde-Lago I, Köhler S, You Y, Dubnovitsky A, Kramer A, Meng F, Zollner V, Vogg L, Ryan TJ, Hanada KI, Regen T, Waisman A, Malmström V, Benson E, Kisielow J, Krey T, Winkler T, Hanke L, Kreslavsky T (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Science American Association for the Advancement of Science

Book Volume: 393

Pages Range: eadx9264-

Journal Issue: 6808

DOI: 10.1126/science.adx9264

Abstract

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 (TH1)-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 with CRIS profile

Lisa Vogg Professur für Genetik Thomas Winkler Professur für Genetik

Involved external institutions

Karolinska University Hospital / Karolinska Universitetssjukhuset SE Sweden (SE) Karolinska Institute SE Sweden (SE) Repertoire Immune Medicines GB United Kingdom (GB) Universität zu Lübeck DE Germany (DE) Trinity College Dublin IE Ireland (IE) National Cancer Institute (NCI) US United States (USA) (US) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE)

How to cite

APA:

Ye, K., Francis, N., Dunst, J., Borgenstam, A., Rocamonde-Lago, I., Köhler, S.,... Kreslavsky, T. (2026). Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of TH1-like γδT cells. Science, 393(6808), eadx9264-. https://doi.org/10.1126/science.adx9264

MLA:

Ye, Kewei, et al. "Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of TH1-like γδT cells." Science 393.6808 (2026): eadx9264-.

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