p53 Specific (auto)immunity in mice
Lauwen, M.M.
Citation
Lauwen, M. M. (2008, October 16). p53 Specific (auto)immunity in mice. Retrieved from https://hdl.handle.net/1887/13147
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/13147
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p53 specific (auto)immunity in mice
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus Prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op 16 oktober 2008 klokke 16.15 uur
door
Marjolein Monique Lauwen
geboren te Borsele
in 1977
Promotiecommissie
Promotor Prof. Dr. C.J.M. Melief Co-promotores Dr. R. Offringa
Dr. S.H. van der Burg
Referent Prof. Dr. M. Theobald
Universitair Medisch Centrum Utrecht
Overige leden Prof. Dr. W.E. Fibbe
Prof. Dr. E.A.J.M. Goulmy
Prof. Dr. J.P. Medema
Academisch Medisch Centrum Universiteit van Amsterdam
Prof. Dr. J. Morreau
Prof. Dr. T.N. Schumacher
Copyright, Marjolein M. Lauwen, 2008
The studies described in this thesis were performed at Leiden University Medical Center, at the department of Immunohematology and Blood Transfusion. Financial support was provided by the Dutch Cancer Society (NKB-KWF), grant nr. 2002- 2735.
Publication of this thesis was financially supported by the Dutch Cancer Society (NKB-KWF), Jurriaanse Stichting, Roche Diagnostics and BD Biosciences.
A vaincre sans péril,
on triomphe sans gloire
Pierre Corneille, le Cid
Table of contents
Chapter 1 Introducti on 7
Chapter 2 Self tolerance does not restrict the CD4+ T-helper response 25 against the p53 tumor anti gen
Chapter 3 Predicti on of the immunogenic potenti al
of frame shift mutated anti gens in microsatellite instable cancer 43 Chapter 4
4.1 Generati on of p53¹⁵⁸⁻¹⁶⁶ T cell receptor transgenic mouse 63 4.2 Tumor eradicati on by p53-specifi c CD8+ T-cells
is accompanied by destructi on
of the hematopoieti c compartment 73 4.3 Retroviral transducti on of p53¹⁵⁸⁻¹⁶⁶ T cell receptor
in naïve splenocytes 97 Chapter 5 Discussion 107 Chapter 6 Nederlandse samenvatti ng (Dutch summary) 121
Curriculum vitae 127