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Cover Page

The handle http://hdl.handle.net/1887/39949 holds various files of this Leiden University dissertation.

Author: Pont, M.J.

Title: Discovery of minor histocompatibility antigens as targets for immunotherapy

Issue Date: 2016-06-07

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DISCOVERY OF

MINOR HISTOCOMPATIBILITY ANTIGENS AS TARGETS FOR IMMUNOTHERAPY

Margot Pont

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Discovery of minor histocompatibility antigens as targets for immunotherapy

© 2016 Margot Pont Amsterdam

Cover image: Kristian Bolk, Mt. Rainier National Park rainforest Layout: Margot Pont, based on design by Liset Westera Printing: Ipskamp, Enschede, The Netherlands

ISBN: 978-94-028-0175-0

The research described in this thesis was performed at the Department of Hematology of the Leiden University Medical Center in Leiden, the Netherlands and was financially supported by the Dutch Cancer Society (UL 2010-4748).

Printing of this thesis was financially supported by Boehringer Ingelheim, Chipsoft, Greiner Bio-One and BD Biosciences.

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Discovery of

minor histocompatibility antigens as targets for immunotherapy

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 7 juni 2016

klokke 15:00 uur door

Margot Jooske Pont

geboren te Leidschendam

in 1986

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Promotor:

Prof. dr. J.H.F. Falkenburg

Co-promotor:

Dr. M. Griffioen

Promotiecommissie:

Prof. dr. S.H. van der Burg

Prof. dr. T.C. de Gruijl, VU Medisch Centrum, Amsterdam

Dr. T. Mutis, VU Medisch Centrum, Amsterdam

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wees niet bang voor al te grote dromen ga als je het zeker weet, en als je aarzelt wacht hoe ijdel zijn de dingen die je je hebt voorgenomen

het mooiste overkomt je, het minste is bedacht

- Freek de Jonge, ‘Kijk, Dat Is Freek’, 2011

To those who made me who I am

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Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Appendices

9

29

73

89

107

139

160 167 169 170

Table of Contents

General introduction and Aim of the study

Microarray gene expression analysis to evaluate cell type specific expression of targets relevant for immunotherapy of hematological malignancies

LB-ARHGDIB-1R as novel minor histocompatibility antigen for therapeutic application

Minor histocompatibility antigen LB-TTK-1D is encoded by an alternative transcript that is degraded by nonsense mediated decay

Integrated whole genome and transcriptome analysis identified a therapeutic minor histocompatibility antigen in a splice variant of ITGB2

Summary and General discussion

Nederlandse samenvatting Dankwoord

Curriculum vitae List of publications

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