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

• DOI: 10.1093/jleuko/qiae184
• Publication Date: 2024-08-26T14:27:43Z
• Authors: Dhwani Radhakrishnan; Jana Kotulová; Lucie Hofmanová; Anjana Anilkumar ...; Marcello Turi; David Žihala; Michal Ďurech; Jan Vrána; Valeria Uleri; Veronika Niederlova; Ondrej Stepanek; Zuzana Chyra; Tomáš Jelínek; Roman Hájek; Matouš Hrdinka
• Keywords: Jurkat cells

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