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

• 成果类型: Article
• 署名作者: Ye, Kewei; Francis, Nimmy; Dunst, Josefine; Borgenstam, Amanda; Rocamonde-Lago, Iris; Koehler, Stefanie; You, Yuanyuan; Dubnovitsky, Anatoly; Kramer, Anja; Meng, Fanxi; Zollner, Valentin; Vogg, Lisa; Ryan, Tomas J.; Hanada, Ken-ichi; Regen, Tommy; Waisman, Ari; Malmstrom, Vivianne; Benson, Erik; Kisielow, Jan; Krey, Thomas; Winkler, Thomas H.; Hanke, Leo; Kreslavsky, Taras
• 署名单位: Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Karolinska University Hospital; University of Chicago; Karolinska Institutet; Karolinska University Hospital; SciLifeLab; Karolinska Institutet; University of Lubeck; Karolinska Institutet; Karolinska University Hospital; University of Erlangen Nuremberg; Trinity College Dublin; Trinity College Dublin; University of Melbourne; Florey Institute of Neuroscience & Mental Health; Canadian Institute for Advanced Research (CIFAR); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; Hannover Medical School; German Center for Infection Research; Hannover Medical School
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adx9264
• 发表日期: 2026-07-16
• 页码: eadx9264
• 关键词: ANTIGEN RECOGNITION; receptor; complex; stress; specificity; expression; selection; effector; binds; interleukin-17

摘要

Of the three classes of lymphocytes that constitute the adaptive immune system, gamma delta T cells are the only class for which the principles of antigen recognition remain enigmatic. Although endogenous gamma delta T cell antigen receptor (gamma delta TCR) ligands are thought to regulate gamma delta T cell development, their identities are largely elusive. Here, we identified the interleukin 17 receptor A chain (IL17RA) as a gamma delta TCR ligand that drove the differentiation of V delta 7+ gamma delta T 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 V delta 7 chain, enabling the selection of cells with a diverse CDR3 repertoire and thus acting as a nonclonotypic gamma delta TCR ligand. Together with the nonclonotypic mode of gamma delta TCR engagement by butyrophilins, these results suggest that such interactions represent a general biological mechanism shaping the gamma delta T cell compartment.