Modeling the MHC-I pathway [Elektronische Ressource] / von Björn Peters

Modeling the MHC-I pathway DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) im Fach Biophysik eingereicht an der Mathematisch-Naturwissenschaftlichen Fakultät I der Humboldt-Universität zu Berlin von Diplom-Physiker Björn Peters geboren am 18.5.1973 in Hamburg Präsident der Humboldt-Universität zu Berlin Prof. Dr. Jürgen Mlynek Dekan der Mathematisch-Naturwissenschaftlichen Fakultät I Prof. Dr. Michael Linscheid Gutachter: 1. Prof. Hermann-Georg Holzhütter 2. Prof. Reinhard Heinrich 3. Prof. Robert Tampe eingereicht am: 24.02.2003 Tag der mündlichen Prüfung: 10.07.2003 2/112 Summary A major task of the immune system is to identify cells that have been infected by a virus or that have mutated, and discriminate them from healthy cells. This duty is assigned to cytotoxic T-lymphocytes (CTL), which scan epitopes presented to them on cell surfaces derived from intracellular proteins through the MHC-I antigen processing pathway. The goal of this work is to provide computational methods that allow to predict which epitopes get presented from the large pool of peptide candidates contained in intracellular proteins. This is achieved by examining the selective influence of three major steps in the pathway: peptide generation by the proteasome, peptide transport into the ER by TAP, and binding of peptides to MHC-I molecules.