Butyrophilin molecules govern γδ T cell reactivity against phosphoantigens
| العنوان: | Butyrophilin molecules govern γδ T cell reactivity against phosphoantigens |
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| المؤلفون: | Marc Rigau, Simone Ostrouska, Tom Fulford, Darryl Neil Johnson, Katherine Woods, Zheng Ruan, Hamish McWilliam, Christopher Hudson, Candani Tutuka, Adam K Wheatley, Stephen J Kent, Jose A Villadangos, Bhupinder Pal, Christian Kurts, Jason Simmonds, Matthias Pelzing, Andrew D Hammet, Anne M Verhagen, Gino Vairo, Eugene Maraskovsky, Con Panousis, Nicholas Anthony Gherardin, Jonathan Cebon, Dale Ian Godfrey, Andreas Behren, Adam Peter Uldrich |
| المصدر: | The Journal of Immunology. 204:140.12-140.12 |
| بيانات النشر: | The American Association of Immunologists, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Humans have a minor lymphocyte population of gamma-delta (γδ) T cells. The majority of these express a recombined Vγ9Vδ2 T cell receptor (TCR) attractive to immunotherapy. This distinct TCR conveys reactivity to phosphorylated antigens (pAg) that derive from pathogens or accumulate inside tumour cells. Such T cell responses are regulated by butyrophilin (BTN) 3A1 and other membrane-related proteins present on antigen-presenting cells. However, the activation mechanism and direct molecular ligand recognised by the γδ TCR remain a crucial unresolved question. Herein, we used pAg-reactive TCR probes in a whole-genome screen to identify BTN2A1 as an essential ligand. In further investigation, we elucidated its functionality working in cis with BTN3A1. Also, a mutational analysis unveiled critical regions of the γδ TCR are positioned at opposite sides. We locate germ-line encoded residues of the Vγ9 chain were responsible for BTN2A1 binding, whereas two amino-acids of the Vδ2 chain were necessary for a complete response to pAg. In conclusion, we propose a dual-ligand complex model that senses pAg to evoke immune responses, wherein BTN2A1 sets the framework to develop new opportunities on γδ T cell-based immunotherapies. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4171696162f3ee8c3009f2fdfd275f60 https://doi.org/10.4049/jimmunol.204.supp.140.12 |
| رقم الأكسشن: | edsair.doi...........4171696162f3ee8c3009f2fdfd275f60 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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