Oral Presentation 24th Annual Lorne Proteomics Symposium 2019

Integrated time-series analysis of proteomic and transcriptomic profiles for activated human T-cell function (#45)

Harshi Weerakoon 1 2 , Ahmed Mohamed 1 , Ailin Lepletier 1 , Jeremy Potriquet 1 3 , Yide Wong 1 3 , Stephen Kazakoff 1 , Pamela Mukhopadhyay 1 , Nic Waddell 1 , John J Miles 1 3 , Jason Mulvenna 1 2 , Michelle M Hill 1
  1. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia
  3. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia

Human T-cells play a pivotal role in adaptive immunity. The two major T cell subsets, CD4+ and CD8+ T cells are defined by expression of distinct T cell receptor (TCR), and perform different functions. Activation of the TCRs triggers proliferation of T cell clones through a complex process of T-cell activation. Transcriptome analysis has been the method of choice to study T cell activation, however, several studies demonstrate poor correlations between the transcriptome and the corresponding proteome in a variety of cells. In this study, we applied a systems biology approach to assess the concordance of temporal profiles of in vitro activated human CD4+ and CD8+ T-cells proteomic and transcriptomic expressions at protein, pathway and network levels. Shotgun proteomics and RNA-sequencing were performed at five different time points following in vitro activation to characterize early (24 hours) and late (24 hours to 7 days) phases of T-cell activation. Strikingly, at 6 hours, only 10% of differentially expressed genes were concordant with differentially expressed proteins. However, 50% of these changes were observed at later time points, indicative of a time-delay for transcriptome changes to be reflected at proteome level. Pathway analysis for proteomics identified activation of cytokine production and protein synthesis pathways during early phase, while late phase pathways were related to glycolysis and mTOR, PI3K and apoptosis signalling. Interestingly, despite the distinct functions of CD4+ and CD8+ T cells, both proteomic and transcriptomic profiling identified similar expression patterns during activation, suggesting a conserved activation process. Nevertheless, specific protein signatures were identified for T cell subsets including specific cytotoxic proteins in CD8+ T cells. In summary, this integrative multi-omic evaluation of T cell activation provides insight into the temporal relationship between transcriptome and proteome. To our knowledge, this is the first study to compare transcriptome and proteome through a time course in T cells.