Antigen-specific CD4+ T cell immunity against Salmonella

Dr Nancy Wang
Department of Microbiology and Immunology, the University of Melbourne, at Peter Doherty Institute for Infection and Immunity
22 March 2019 - 3:00pm
Rountree Room 356, Level 3, Biological Sciences Building D26

CD4+ T cells play a pivotal role in host defence against many important intracellular bacterial infections, and orchestrate cellular and humoral immune responses for bacterial clearance.  Bacterial proteomes typically consist of thousands of proteins, so the question of how CD4+ T cells select immunodominant antigens to confer effective immunity is central to the rational design of virtually all vaccines.  Salmonella enterica serovar Typhimurium is arguably one of the best-established models for studying CD4+ T cell immunity.  In humans, and in murine infection models, CD4+ T cells are essential for the clearance of the primary infection and confer significant protection against re-infection.  With the recent identification of a Salmonella immunopeptidome as is presented by MHC-II during murine infection, this seminar will explore new opportunities for defining the ‘selection criteria’ by which a small subset of protein antigens become immunodominant and induce protective CD4+ T cell responses during bacterial infection.  This has enabled the discussion of some key questions, such as whether there are identifiable commonalities between immunodominant CD4+ T cell epitopes, or whether epitope identity confers differential effector/memory CD4+ T cell development.  The ultimate goal is to provide a paradigm for antigen selection mechanisms that are broadly applicable to CD4+ T cell-mediated immunity against Salmonella and other complex pathogens. 

Biography: Nancy obtained her PhD from the University of Melbourne (UoM) in 2013, under joint supervision from Dr Tom Brodnicki (WEHI and St Vincent’s Institute) and A/Prof Odilia Wijburg (UoM).  During this time, she characterised a novel genetic switch point influencing both immunity against Listeria infection and susceptibility to autoimmune diabetes in murine models.  Since her PhD completion, Nancy has been a postdoc in Prof Dick Strugnell’s group at the Department of Microbiology and Immunology, UoM.  Her research interest is to understand the mechanisms of protective immunity against bacterial pathogens, principally Salmonella, but also extends to Klebsiella and Listeria.  She has recently spent several months working in collaborating laboratories at the Wellcome Trust Sanger Institute (Cambridge, UK), the Weatherall Institute at Oxford University (Oxford, UK) and the LIMES Institute (Bonn, Germany).  Utilising the unique tools and expertise from collaborating laboratories, her current work aims to investigate the key mechanisms by which a small subset of protein antigens become immunodominant and induce protective CD4+ T cell responses during bacterial infection.  This work was seed-funded by the UoM Early Career Development Grant Scheme in 2018.