Academic Journal
TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation
| العنوان: | TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation |
|---|---|
| المؤلفون: | Worboys, Jonathan D., Vowell, Katherine N., Hare, Roseanna K., Ambrose, Ashley R., Bertuzzi, Margherita, Conner, Michael A., Patel, Florence P., Zammit, William H., Gali-Moya, Judit, Hazime, Khodor S., Jones, Katherine L., Rey, Camille, Jonjić, Stipan, Roviš, Tihana Lenac, Tannahill, Gillian M., Cruz De Matos, Gabriela Dos Santos, Waight, Jeremy D., Davis, Daniel M. |
| المصدر: | https://www.nature.com/articles/s41467-023-40755-3 ; Nature Communications ; Volume 14 ; Issue 1 ; ISSN 2041-1723 (Online. |
| سنة النشر: | 2023 |
| المجموعة: | Repository of the University of Rijeka |
| مصطلحات موضوعية: | BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences |
| الوصف: | TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell intrinsic inhibitory signals in T cells remains unclear. Here we show, by ana lysing lymphocytes from matched human tumour and peripheral blood sam ples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT’s intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting indepen dently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Sveučilište u Rijeci. Medicinski fakultet. Centar za proteomiku.; University of Rijeka. Faculty of Medicine. Center for Proteomics.; https://www.unirepository.svkri.uniri.hr/islandora/object/medri:8048; https://urn.nsk.hr/urn:nbn:hr:184:636511; https://www.unirepository.svkri.uniri.hr/islandora/object/medri:8048/datastream/FILE0 |
| الاتاحة: | https://www.unirepository.svkri.uniri.hr/islandora/object/medri:8048 https://urn.nsk.hr/urn:nbn:hr:184:636511 https://www.unirepository.svkri.uniri.hr/islandora/object/medri:8048/datastream/FILE0 |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.7AE0BF7C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |