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The handle http://hdl.handle.net/1887/22802 holds various files of this Leiden University dissertation

Author: Cunha Oliveira, Claudia da

Title: Alternative antigen processing and presentation pathways by tumors

Issue Date: 2013-12-10

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ALTERNATIVE ANTIGEN PROCESSING AND PRESENTATION PATHWAYS BY TUMORS

Cláudia da Cunha Oliveira

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The studies described in this thesis were performed in the department of Clinical Oncology at the Leiden University Medical Center and was funded by the Portuguese Foundation For Science and Technology (MCTES) Portugal (SFRH/BD/33539/2008) and AICR (association for international cancer research) nr. 09-776.

Niets in deze uitgave mag worden verveelvoudigd en/of openbaar gemaakt worden zonder voorafgaande schriftelijke toestemming van de auteur.

No part of this thesis may be reproduced in any form without written permission from the author.

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ALTERNATIVE ANTIGEN PROCESSING AND PRESENTATION PATHWAYS BY TUMORS

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 10 december 2013

klokke 10.00 uur door

Cláudia da Cunha Oliveira

geboren te Amares in 1985

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Overige leden Prof. Dr. F. Ossendorp

Prof. Dr. J.J. Neefjes (NKI, Amsterdam) Prof. Dr. M. Yazdanbakhsh

Prof. Dr. G. J. Adema (RU, Nijmegen) Prof. Dr. F. Koning

Dr. E.J.A.M. Sijts (UMC, Utrecht)

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| TABLE OF CONTENTS

Chapter 1 Introduction 7

Chapter 2 Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I

peptide repertoires 23

Chapter 3 New role of signal peptide peptidase to liberate C-terminal

peptides for MHC class-I presentation 47

Chapter 4 The proteasome strongly contributes to the TAP-independent

peptide repertoire presented by MHC-I 75

Chapter 5 The nonpolymorphic MHC Qa-1

b

mediates CD8

+

T cell s

urveillance of antigen-processing defects 93

Chapter 6 The other Janus face of Qa-1 and HLA-E: diverse peptide

repertoires in times of stress 119

Chapter 7 Discussion 137

Nederlandse samenvatting 153

Curriculum vitae 157

List of publications 159

Acknowledgements 161

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