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

While endogenous γδTCR ligands are thought to regulate γδT cell development, their identities are largely elusive. Here, we identified the cytokine receptor chain IL17RA as a γδTCR ligand that drove the differentiation of Vδ7+ γδT cells with a TH1-like effector program.

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 – therefore acting as a non-clonotypic γδTCR ligand. Together with the non-clonotypic mode of γδTCR engagement by butyrophilins, these results suggest that such interactions represent a general biological mechanism shaping the γδT cell compartment.