Immune sensing of non-peptidic antigens

Rossjohn J1,2,3

  1. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  2. ARC Centre of Excellence in Advanced Molecular Imaging, Monash University.
  3. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

The immune system is key to our survival as the human population is constantly under threat from devastating pathogens. Humans defend themselves from microbes by mounting protective immune responses that include activating the innate and adaptive arms of the cellular immune system. Conversely, while cellular immunity is critical to our survival, immune dysfunction is a major contributor to disease burden globally. Major advances in understanding the immune system are beginning to impact on human health through novel immunotherapies. Nonetheless, there are many aspects of human immunity we do not understand. T cells, via their T cell receptor (TCR) expressed on its cell surface, play a critical role in mediating cellular immunity. While is generally considered that TCRs interacts with peptide antigens bound to the Major Histocompatibility Complex (MHC), TCRs also interact with lipid-based Ags bound by CD1 family members. Using a combination of chemical, structural and immunological approaches, we have also established how T cells, termed MAIT cells, can recognise microbial-based vitamin B metabolites. I shall detail the structural basis of immune sensing of non-peptidic antigens.