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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

Note: To cite this publication please use the final published version (if applicable).

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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

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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.

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A vaincre sans péril,

on triomphe sans gloire

Pierre Corneille, le Cid

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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

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