Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of T <sub>H</sub> 1-like γδT cells
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 (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.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (23)
Kewei Ye
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Nimmy Francis
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Josefine Dunst
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Amanda Borgenstam
Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Iris Rocamonde-Lago
Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Stefanie Köhler
Institute of Biochemistry, Center of Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
Yuanyuan You
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Anatoly Dubnovitsky
Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Anja Kramer
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Fanxi Meng
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Valentin Zollner
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Lisa Vogg
Division of Genetics, Department Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Tomás J. Ryan
Ken-ichi Hanada
Surgery Branch, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Tommy Regen
Institute for Molecular Medicine and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
Ari Waisman
Institute for Molecular Medicine and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
Vivianne Malmström
Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Erik Benson
Science for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Jan Kisielow
Repertoire Immune Medicines, Schlieren, Switzerland.
Thomas Krey
Institute of Biochemistry, Center of Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
Thomas H. Winkler
Division of Genetics, Department Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Leo Hanke
Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Taras Kreslavsky
Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.