In higher organisms, cells present epitopes, which are small fragments derived from proteins, on their cell surface. Thereby, they enable Cytotoxic T Cells to monitor and control these cells for expression of bacterial or other non-healthy proteins. We develop models for the main steps in the MHC Class I presentation pathway including the degradation of proteins by the proteasome, transport of peptides into the ER by TAP, binding of epitopes to MHC I molecules and peptid degradation by cytosolic and endoplasmatic aminopeptidases. These model modules allow for prediction of antigenes from protein sequence and are basic for approaches to kinetic modeling of the pathway.
Researchers
Prof. Hermann-Georg Holzhütter
Sascha Bulik
Dr. Björn Peters
in cooperation with Prof. Kloetzel’s group (K. Janek, U Kuckelkorn)
Publications
Schatz MM, Peters B, Akkad N, Ullrich N, Martinez AN, Carroll O, Bulik S, Rammensee HG, van Endert P, Holzhütter HG, Tenzer S, Schild H. (2008) Characterizing the N-terminal processing motif of MHC class I ligands. J Immunol., 180(5):3210-7. [PubMed]
Bulik S, Peters B, Holzhütter HG. (2005) Quantifying the contribution of defective ribosomal products to antigen production: a model-based computational analysis. J Immunol., 175(12):7957-64. [PubMed]
Tenzer S, Peters B, Bulik S, Schoor O, Lemmel C, Schatz MM, Kloetzel PM, Rammensee HG, Schild H, Holzhütter HG. (2005). Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding. Cell. Mol. Life Sci., 62(9), 1025-37. [PubMed]
Bulik S, Peters B, Ebeling C, Holzhütter HG. (2004) Cytosolic processing of proteasomal cleavage products can enhance the presentation efficiency of MHC-1 epitopes. Genome Inform Ser Workshop Genome Inform, 15(1), 24-34. [PubMed]
Peters B, Bulik S, Tampe R, van Endert PM, and Holzhütter HG. (2003) Identifying MHC-I epitopes by predicting the TAP transport efficiency of epitope precursors. J. Immunol., 171(4), 1741-1749. [PubMed]
Peters B, Tong W, Sidney J, Sette A and Weng Z. (2003) Examining the Independent Binding Assumption for Binding of Peptide Epitopes to MHC-I Molecules. Bioinformatics 19(14), 1765-1772. [PubMed]
Peters B, Janek K, Kuckelkorn U and Holzhütter HG. (2002) Assessment of proteasomal cleavage probabilities from kinetic analysis of time-dependent product formation. J. Mol. Biol., 318, 847-862. [PubMed]
Holzhütter HG, Frommel C and Kloetzel PM. (1999) A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20 S proteasome. J. Mol. Biol., 286(4), 1251-65. [PubMed]