Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2021

Mapping single IAV-specific killer T cell transcriptional heterogeneity after infection and vaccination (#72)

Jasmine Li 1 , Adele Barugahare 1 2 , Vibha Udupa 1 , Michael Flossdorf 3 , Yuyin Xie 1 , Patrick Gunther 4 , Moshe Olshanksy 1 , Stephen Turner 5
  1. Department of Microbiology, Biomedical Discovery Institute, Monash University, Melbourne, VIC, Australia
  2. Bioinformatics Platform, Biomedical Discovery Institute, Monash University, Melbourne, VIC, Australia
  3. Technical University, Munich, Germany
  4. Life and Medical Sciences Institute, University of Bonn, Bonn
  5. Microbiology and Immunology, Doherty Institute, University of Melbourne, Parkville, VIC, Australia

The establishment of an effective memory T cell population is critical for providing a host with protection from subsequent pathogen re-infection and underpins all effective vaccine strategies.  Despite intense study, exactly when memory T cell formation occurs, and the precise factors that drive this process are still be elucidated. To address these questions, we  performed extensive single cell RNA-seq (scRNA-seq) on naive, effector (day 3 to 20) and memory influenza A virus (IAV) CD8+ T cells to ask how transcriptional heterogeneity at the single cell level impacts the generation of effective IAV-specific CD8+ T cell immunity. We generated scRNA-seq data and scATAC-seq data from a total of ~36K and 10K cells, respectively.  We utilised RNA-velocity analysis to generate cellular trajectories and demonstrated that memory T cell formation is generated in the earliest divisions after T cell activation. Interrogation of transcriptional patterns identified cell division rate as a key factor that determines whether a cell becomes an effector vs memory T cells. To better understand factors that restrain T cell division, we identified key chromatin modifiers appear to regulate early cell division and hence memory T cell differentiation. This approach has the potential to identify novel regulators of the memory state that may be future targets for modulation to promote effective T cell memory.