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Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation

D. Radhakrishnan, J. Kotulová, L. Hofmanová, AA. Sithara, M. Turi, D. Žihala, M. Ďurech, J. Vrána, V. Uleri, V. Niederlova, O. Stepanek, Z. Chyra, T. Jelínek, R. Hájek, M. Hrdinka

. 2024 ; 117 (1) : . [pub] 20241231

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25010541

Grantová podpora
GA CR 21-21413S Czech Science Foundation
Ministry of Health of the Czech Republic-Conceptual Development of Research Organization
404222 Charles University Grant Agency
Ministry of Education, Youth, and Sports
CZ.02.01.01/00/22_008/0004644 Czech Republic OP JAK SALVAGE
Ministry of the Environment of the Czech Republic
CZ.10.03.01/00/22_003/0000003 European Union under the LERCO
Operational Programme Just Transition
Specific University Research Grant
Ministry of Education, Youth and Sports of the Czech Republic in the year 2023
Interní grantová soutěž pro studenty doktorského studia na Ostravské univerzitě
Science and research in Mo-644 Moravian-Silesian Region 2021
CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium
CEITEC Proteomics Core Facility
ID:90254 e-INFRA CZ

The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into the role of in T cell immunity, focusing on T cell-B cell conjugate formation and T cell activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes in Jurkat T cells, we identified BAP1 as a key positive regulator of T cell-B cell conjugate formation. Subsequent investigations into BAP1 knockout cells revealed impaired T cell activation, evidenced by decreased MAPK and NF-kB signaling pathways and reduced CD69 expression upon T cell receptor stimulation. Flow cytometry and qPCR analyses demonstrated that BAP1 deficiency leads to decreased surface expression of T cell receptor complex components and reduced mRNA levels of the co-stimulatory molecule CD28. Notably, the observed phenotypes associated with BAP1 knockout are specific to T cells and fully dependent on BAP1 catalytic activity. In-depth RNA-seq and mass spectrometry analyses further revealed that BAP1 deficiency induces broad mRNA and protein expression changes. Overall, our findings elucidate the vital role of BAP1 in T cell biology, especially in T cell-B cell conjugate formation and T cell activation, offering new insights and directions for future research in immune regulation.

Citace poskytuje Crossref.org

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