Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation

• Published in: NPJ systems biology and applications Vol. 10; no. 1; pp. 21 - 13
• Main Authors: Weerakoon, Harshi, Mohamed, Ahmed, Wong, Yide, Chen, Jinjin, Senadheera, Bhagya, Haigh, Oscar, Watkins, Thomas S., Kazakoff, Stephen, Mukhopadhyay, Pamela, Mulvenna, Jason, Miles, John J., Hill, Michelle M., Lepletier, Ailin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/553; Bioinformatics; Biomedical and Life Sciences; CD28 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Cell activation; Cell proliferation; Chemokines; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Cytotoxicity; Down-regulation; Glucose transport; Life Sciences; Lymphocytes; Lymphocytes T; Proteomes; Proteomics; Systems Biology; T cell receptors; Transcription factors; Transcriptomes; Transcriptomics
• ISSN: 2056-7189; 2056-7189
• DOI: 10.1038/s41540-024-00346-4

Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human CD4 and CD8 T cells following ex vivo stimulation with anti-CD3/CD28 beads, which revealed major transcriptome-proteome uncoupling. The early activation phase in both CD4 and CD8 T cells was associated with transient downregulation of the mRNA transcripts and protein of the central glucose transport GLUT1. In the proliferation phase, CD4 and CD8 T cells became transcriptionally more divergent while their proteome became more similar. In addition to the kinetics of proteome-transcriptome correlation, this study unveils selective transcriptional and translational metabolic reprogramming governing CD4 and CD8 T cell responses to TCR stimulation. This temporal transcriptome/proteome map of human T cell activation provides a reference map exploitable for future discovery of biomarkers and candidates targeting T cell responses.