Transcriptional reprogramming via signaling domains of CD2, CD28, and 4-1BB

Journal article

Costimulatory signals provided to T cells during antigen encounter have a decisive role in the outcome of immune responses. Here, we used chimeric receptors harboring the extracellular domain of mouse inducible T cell costimulator (mICOS) to study transcriptional activation mediated by cytoplasmic sequences of the major T cell costimulatory receptors CD28, 4-1BB, and CD2. The chimeric receptors were introduced in a T cell reporter platform that allows to simultaneously evaluate nuclear factor κB (NF-κB), NFAT, and AP-1 activation. Engagement of the chimeric receptors induced distinct transcriptional profiles. CD28 signaling activated all three transcription factors, whereas 4-1BB strongly promoted NF-κB and AP-1 but downregulated NFAT activity. CD2 signals resulted in the strongest upregulation of NFAT. Transcriptome analysis revealed pronounced and distinct gene expression signatures upon CD2 and 4-1BB signaling. Using the intracellular sequence of CD28, we exemplify that distinct signaling motifs endow chimeric receptors with different costimulatory capacities.

Authors: De Sousa Linhares, A; Sharma, S; Steinberger, P; Leitner, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: iScience
• Volume: 27
• Issue: 3
• Article number: 109267
• Publication date: 2024-02-19
• Acceptance date: 2024-02-14
• DOI: 10.1016/j.isci.2024.109267
• EISSN: 2589-0042
• Pmid: 38455974
• Language: English
• Keywords: omics; transcriptomics; molecular biology