Project (Juliane Liepe)

The Quantitative and Systems Biology group employs in silico approaches, using in vitro and ex vivo and in vivo experimental data, to study the pathways of the proteasome that regulate the human immune response.
The proteasome is a multicomplex enzyme that catalyses protein degradation. Apart from its function in protein metabolism, the proteasome regulates the immune system through antigen presentation, where the proteasome produces most of the epitopes presented in the MHC-class I pathway. These epitopes can be generated by simple cut, or cut-and-paste events. Latter so-called proteasome-generated spliced peptides (PSPs) represent more than one third of all epitopes bound to MHC-class I molecules.

• Specht, G.; Roetschke, H. P.; Mansurkhodzhaev, A.; Henklein, P.; Textoris-Taube, K.; Urlaub, H.; Mishto, M.; Liepe, J.: Large database for the analysis and prediction of spliced and non-spliced peptide generation by proteasomes. Scientific Data 7, 146 (2020)
  
  
• Mishto, M.; Mansurkhodzhaev, A.; Ying, G.; Bitra, A.; Cordfunke, R. A.; Henze, S.; Paul, D.; Sidney, J.; Urlaub, H.; Neefjes, J. et al.: An in silico-in vitro pipeline identifying an HLA-A*02:01+ KRAS G12V+ spliced epitope candidate for a broad tumor-immune response in cancer patients. Frontiers in Immunology 10, 2572 (2019)
  
  
• Liepe, J.; Sidney, J.; Lorenz, F. K. M.; Sette, A.; Mishto, M.: Mapping the MHC class I spliced immunopeptidome of cancer cells. Cancer Immunology Research 7 (1), pp. 62 - 76 (2019)
  
  
• Kuckelkorn, U.; Stübler, S.; Textoris-Taube, K.; Killian, C.; Niewienda, A.; Henklein, P.; Janek, K.; Stumpf, M. P.; Mishto, M.; Liepe, J.: Proteolytic dynamics of human 20S thymoproteasome. Journal of Biological Chemistry 294, pp. 7740 - 7754 (2019)
  
  
• Liepe, J.; Marino, F.; Sidney, J.; Jeko, A.; Bunting, D. E.; Sette, A.; Kloetzel, P. M.; Stumpf, M.l. P. H.; Heck, A. J. R.; Mishto, M.: A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science 354 (6310), pp. 354 - 358 (2016)