Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Mass spectrometry– teaching us new lessons in immunity (#44)

Anthony Purcell 1 2
  1. Monash University , Clayton, VIC, Australia
  2. Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia

Immunopeptidomics is the study of the repertoire of peptide ligands selected for antigen presentation by MHC class 1 molecules. In recent years, this has been revolutionised by the use of in depth qualitative and quantitative mass spectrometry techniques. In particular, fundamental and novel insights have been made that shed light on the dynamic range of antigen presentation, the role of HLA polymorphism, antigen presenting cell type and mode of antigen processing on the resultant immunopeptidome, as well as diversity introduced by degenerate proteolysis and extensive post-translational modifications. I will highlight recent advances in analytical workflows and how these have provided new insights into antigen processing and presentation by selecting recent published and unpublished examples from our laboratory (1-7).


  1. Illing, P. T. et al. HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome. Nature communications 9, 4693 (2018).
  1. Pymm, P. et al. MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape. Nat Struc Mol Biol 24, 387-94 (2017).
  1. Ooi, J. D. et al. Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells. Nature 545, 243-7 (2017).
  2. Faridi, P. et al. A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands. Science Immunol 3, pii: eaar3947 (2018).
  1. Croft, N. P. et al. Most viral peptides displayed by class I MHC on infected cells are immunogenic. Proc Natl Acad Sci U S A, 116:3112-17 (2019).
  1. Koutsakos, M et al. Human CD8+ T cell cross-reactivity across influenza A, B and C viruses, Nat Immunol, 20:613-25 (2019)
  2. Woods, K. et al. The diversity of the immunogenic components of the melanoma immunopeptidome, bioRxiv, https://doi.org/10.1101/623223 (2019)