The glyco-immunopeptidome – mining an untapped resource for immunotherapy

The presentation of post-translationally modified (PTM) peptides by cell surface MHC molecules increases the diversity of targets for recognition by T cells. Our understanding of the range and types of PTMs presented in this manner is largely restricted to small structural changes such as phosphorylation, deamidation and citrullination. Far less understood is the potential presentation of peptides modified by glycosylation [4], one of the most common PTMs occurring on proteins. Given that dysregulated or aberrant protein glycosylation is associated with many disease states including cancer, improving our knowledge of the glyco-immunopeptidome will greatly assist in the identification of novel T cell targets. This project will encompass mining of existing MHC immunopeptidome datasets—as well as the generation of new datasets in the lab—to identify and characterize the frequency and diversity of glycopeptides presented by MHC class I and II molecules and how these may form novel targets for T cells. In concert, the study will be complemented with a detailed analysis of the whole cell glycoproteome in collaboration with the Analytical Glycoimmunology group headed by Dr Morten Thaysen Andersen, Macquarie University, Sydney. The prospective student will get the opportunity to spend time in Dr Thaysen Andersen’s laboratory and garner invaluable skills in glycomics and glycoproteomics. References 1. Croft et al. (2019) Proc Natl Acad Sci U S A. [PMID: 30718433] 2. Wu et al. (2019) Nat Commun. [PMID: 31253788] 3. Faridi et al. (2018) Sci Immunol. [PMID: 30315122] 4. Malakar et al. (2017). J Proteome Res. [PMID: 27550523]