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

J 2024

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

RADHAKRISHNAN, Dhwani; Jana KOTULOVA; Lucie HOFMANOVA; Anjana Anilkumar SITHARA; Marcello TURI et al.

Základní údaje

Originální název

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

Autoři

Vydání

Journal of Leukocyte Biology, New York, Society for Leukocyte Biology, 2024, 0741-5400

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.100

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90242/24:00143941

Organizační jednotka

CIISB III

Klíčová slova anglicky

BAP1; CRISPR-Cas9 screening; T cell activation; T cell receptor (TCR); T cell-B cell conjugates

Štítky

CF PROT, ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 11. 3. 2026 14:30, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

90242, velká výzkumná infrastruktura

Název: CIISB III

Citovat

RADHAKRISHNAN, Dhwani; Jana KOTULOVA; Lucie HOFMANOVA; Anjana Anilkumar SITHARA; Marcello TURI; David ZIHALA; Michal DURECH; Jan VRANA; Valeria ULERI; Veronika NIEDERLOVA; Ondrej STEPANEK; Zuzana CHYRA; Tomas JELINEK; Roman HAJEK a Matous HRDINKA. Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation. Journal of Leukocyte Biology. New York: Society for Leukocyte Biology, 2024, roč. 117, č. 1, s. 1-12. ISSN 0741-5400. Dostupné z: https://doi.org/10.1093/jleuko/qiae184.

@article{2559758,
   author = {Radhakrishnan, Dhwani and Kotulova, Jana and Hofmanova, Lucie and Sithara, Anjana Anilkumar and Turi, Marcello and Zihala, David and Durech, Michal and Vrana, Jan and Uleri, Valeria and Niederlova, Veronika and Stepanek, Ondrej and Chyra, Zuzana and Jelinek, Tomas and Hajek, Roman and Hrdinka, Matous},
   article_location = {New York},
   article_number = {1},
   doi = {https://doi.org/10.1093/jleuko/qiae184},
   keywords = {BAP1; CRISPR-Cas9 screening; T cell activation; T cell receptor (TCR); T cell-B cell conjugates},
   language = {eng},
   issn = {0741-5400},
   journal = {Journal of Leukocyte Biology},
   title = {Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation},
   url = {https://watermark02.silverchair.com/qiae184.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA3IwggNuBgkqhkiG9w0BBwagggNfMIIDWwIBADCCA1QGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMkqlb4jEzd0-gjHS_AgEQgIIDJcQtq-mCK2G4ymWrRBiTHRL2gd5Qiv6yKbqsxphjpn1f},
   volume = {117},
   year = {2024}
}

TY  - JOUR
ID  - 2559758
AU  - Radhakrishnan, Dhwani - Kotulova, Jana - Hofmanova, Lucie - Sithara, Anjana Anilkumar - Turi, Marcello - Zihala, David - Durech, Michal - Vrana, Jan - Uleri, Valeria - Niederlova, Veronika - Stepanek, Ondrej - Chyra, Zuzana - Jelinek, Tomas - Hajek, Roman - Hrdinka, Matous
PY  - 2024
TI  - Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation
JF  - Journal of Leukocyte Biology
VL  - 117
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - Society for Leukocyte Biology
SN  - 07415400
KW  - BAP1
KW  - CRISPR-Cas9 screening
KW  - T cell activation
KW  - T cell receptor (TCR)
KW  - T cell-B cell conjugates
UR  - https://watermark02.silverchair.com/qiae184.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA3IwggNuBgkqhkiG9w0BBwagggNfMIIDWwIBADCCA1QGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMkqlb4jEzd0-gjHS_AgEQgIIDJcQtq-mCK2G4ymWrRBiTHRL2gd5Qiv6yKbqsxphjpn1f
N2  - 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.
ER  -

RADHAKRISHNAN, Dhwani; Jana KOTULOVA; Lucie HOFMANOVA; Anjana Anilkumar SITHARA; Marcello TURI; David ZIHALA; Michal DURECH; Jan VRANA; Valeria ULERI; Veronika NIEDERLOVA; Ondrej STEPANEK; Zuzana CHYRA; Tomas JELINEK; Roman HAJEK a Matous HRDINKA. Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation. \textit{Journal of Leukocyte Biology}. New York: Society for Leukocyte Biology, 2024, roč.~117, č.~1, s.~1-12. ISSN~0741-5400. Dostupné z: https://doi.org/10.1093/jleuko/qiae184.

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