Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation
Language English Country Great Britain, England Media print
Document type Journal Article
Grant support
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
PubMed
39189628
DOI
10.1093/jleuko/qiae184
PII: 7742416
Knihovny.cz E-resources
- Keywords
- BAP1, CRISPR-Cas9 screening, T cell activation, T cell receptor (TCR), T cell-B cell conjugates,
- MeSH
- Lymphocyte Activation * immunology MeSH
- B-Lymphocytes * immunology metabolism MeSH
- Jurkat Cells MeSH
- Humans MeSH
- Tumor Suppressor Proteins * metabolism genetics MeSH
- Receptors, Antigen, T-Cell * metabolism MeSH
- Signal Transduction MeSH
- T-Lymphocytes * immunology metabolism MeSH
- Ubiquitin Thiolesterase * genetics metabolism deficiency MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- BAP1 protein, human MeSH Browser
- Tumor Suppressor Proteins * MeSH
- Receptors, Antigen, T-Cell * MeSH
- Ubiquitin Thiolesterase * MeSH
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.
Candiolo Cancer Institute FPO IRCCS Strada Provinciale 142 KM 3 95 10060 Candiolo Italy
Faculty of Science University of Ostrava 30 dubna 22 701 03 Ostrava Czech Republic
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