Oral Presentation 11th Australian Peptide Conference 2015

Differences that matter: Heterogeneity in the immunopeptidome impact of susceptibility and severity of disease. (#29)

Anthony W Purcell 1
  1. Monash University , Clayton, VIC, Australia

Our ability to characterise the products of antigen processing and presentation is now unprecedented with great advances in the qualitative and quantitative analysis of the immunopeptidome. The combination of efficient chromatographic separation and high resolution ultrafast LC-MS/MS allows us to appreciate the impact of the heterogeneity of peptide processing, antigen post-translational modification and the influence of drugs and metabolites on the outcome of disease at the molecular level. I will discuss examples of how heterogeneity in antigens and their processing impacts on the composition of the immunopeptidome and how this then relates to disease outcome. Such studies provide definitive quantitative data to understand the mechanism of human autoimmune diseases like Type 1 Diabetes and Rheumatoid arthritis and susceptibility to pathogens such as Salmonella and Human Immunodeficiency Virus (1-7).

 

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3.            P. T. Illing et al., Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486, 554-558 (2012).

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5.            S. W. Scally et al., A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med 210, 2569-2582 (2013).

6.            R. B. Schittenhelm, T. C. Lim Kam Sian, P. G. Wilmann, N. L. Dudek, A. W. Purcell, Revisiting the arthritogenic peptide theory: Quantitative not qualitative changes in the peptide repertoire of HLA-B27 allotypes. Arthritis & Rheumatology 67, 702-13 (2014).

7.            N. P. Croft et al., Simultaneous quantification of viral antigen expression kinetics using data-independent mass spectrometry. Mol Cell Proteomics 14, 1361-72 (2015).