Oral Presentation 24th Annual Lorne Proteomics Symposium 2019

Systems immunology reveals the importance of direct and cross-presentation in driving cytotoxic T lymphocyte responses to distinct epitopes (#44)

Ting Wu 1 , Jing Guan 1 , Andreas Handel 2 , David C Tscharke 3 , John Sidney 4 , Alessandro Sette 4 , Linda M Wakim 5 , Xavier Y. X. Sng 1 , Paul G Thomas 6 , Anthony W Purcell 1 , Nicole L La Gruta 1 , Nathan P Croft 1
  1. Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  2. Department of Epidemiology and Biostatistics, Health Informatics Institute and Center for the Ecology of Infectious Diseases, University of Georgia, Athens, Georgia, 30602, USA
  3. John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
  4. La Jolla Institute for Allergy and Immunology, La Jolla, California, USA
  5. Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  6. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

The magnitude of CD8+ T lymphocyte (CTL) responses to infection are a function of a multitude of factors that include the available naïve T cell repertoire combined with the context and duration of antigen presentation. Measurement of these factors therefore allows an assessment of their contribution to – and ultimately a chance to model and predict – immunogenicity. Here, we present systems immunology dissection into influenza A virus and vaccinia virus immune responses in mice, notably including targeted mass spectrometry to quantify the impact between direct- and cross-presentation of peptides to drive CTL responses as well as correlates between cell line measurements and those taken ex vivo from infected mice. Together, these data have helped to train mathematical models that delineate the relative importance of these factors and provide a critical step towards predicting immunogenicity. This study highlights how high quality quantitative proteomics and peptidomics data are pivotal in unravelling the complex ecosystem of immune responses to viruses and provides the foundation for the rational design of interventional and therapeutic strategies for viruses that remain a serious threat to humankind.