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1 Cover Page The handle holds various files of this Leiden University dissertation. Author: Hombrink, Pleun Title: Identification of minor histocompatibility antigens by reverse immunology Issue Date:
2 Dankwoord Op een vroege decemberochtend in 2011 kreeg ik vlak voor mijn eerste praatje op het grootste internationale hematologiecongres een belangrijk advies. Houdt de spanning tot het einde vast en laat deze niet direct los bij het uitspreken van je laatste woorden, een goed optreden tijdens de vragenronde bepaalt hoe je bij het publiek blijft hangen. Ondanks een grote dosis gezonde spanning ging mijn presentatie inclusief vragenronde goed en ik denk nog vaak met plezier terug aan deze indrukwekkende tijd. Dit advies heb ik ook proberen te volgen bij het afronden van mijn promotietraject. Het was niet altijd eenvoudig om in de twee jaar sinds mijn vertrek uit Leiden mijn energie te doseren en verdelen om tot een goed resultaat te komen. Het advies bleek wederom waardevol en ik ben trots op het resultaat, mijn proefschrift is klaar! Allereerst wil ik graag mijn collega s bedanken van het laboratorium voor Experimentele Hematologie en in het bijzonder die uit 37 voor de geweldige sfeer die ik daar heb ervaren. Het was geweldig om te beleven hoe in het bijzonder de oudgedienden een hechte en warme groep vormen waar de nieuwe PhD studenten zich meteen thuis voelen. Adviezen en ervaringen werden met veel enthousiasme gedeeld en tijdens de koffiepauze op de brug werden naast de dagelijkse belevenissen ook vaak de saillantste details besproken. Michel Kester wil ik speciaal bedanken voor onze geweldige samenwerking gedurende mijn gehele promotietraject. Door onze discussies heb je mijn enthousiasme vergroot voor de wetenschap en vooral voor het biochemische groffuh gooi- en smijtwerk waar je echt een kei in bent. Lorenz Jahn wil ik bedanken voor de enorme berg werk die hij verzet heeft tijdens zijn stage en de manier waarop hij hiermee later als PhD student is doorgegaan. Heren, naast goede collega s zijn we ook vrienden geworden en ik ben er trots op straks aan jullie zijde op het Rapenburg te mogen staan. Daarnaast wil ik alle co-auteurs danken voor hun belangrijke bijdrage aan het tot stand komen van de hoofdstukken. In het bijzonder mijn eerste student Yotam Raz. Ik heb je tijdens je vrijwillige stage van puber zien opgroeien tot enthousiaste onderzoeker en ik weet zeker dat je een groot onderzoeker gaat worden. I thank Sine Reker Hadrup. As an experienced Postdoc you took me by the hand during the first difficult phase of my PhD. You showed me the great things that can be done using multi-color flow cytometry that I am still doing today. Thanks for inviting me at your lab in Copenhagen and for having me as a guest at your house. Dankwoord Mijn ouders wil ik bedanken voor hun onvoorwaardelijke steun en liefde. Ik heb jullie geduld op de proef gesteld maar dit leidde alleen maar tot meer aanmoedigingen. Lieve Liset, met jou is het iedere dag genieten. Fijn dat we elkaar zo goed begrijpen. Zonder jouw hulp was dit boekje nooit op tijd afgekomen. Op de volgende berg staan we samen! 179
3 180
4 Curriculum vitae Pleun Hombrink werd geboren op 28 juli 1982 te Eindhoven. Na het behalen van het VWO diploma aan het Over Betuwe College te Bemmel in 2001, begon hij in datzelfde jaar met de studie Biomedische wetenschappen aan de Universiteit Utrecht. In 2004 behaalde hij zijn Bachelor of Science titel en begon aan de master Immuniteit en Infectie aan de Universiteit Utrecht. Na een masterstage bij de afdeling Pediatrische Immunologie van het Wilhelmina Kinderziekenhuis, Universitair Medisch Centrum Utrecht (Prof. Dr. A.B.J.Prakken) en een tweede masterstage bij de afdeling Experimentele Virologie van het Academisch Medisch Centrum in Amsterdam (Dr. A.T. Das) behaalde hij in 2006 de Master of Science titel. Vervolgens werd vanaf 2007 tot heden het in dit proefschrift beschreven promotieonderzoek uitgevoerd op het Laboratorium voor Experimentele Hematologie in het Leids Universitair Medisch Centrum onder leiding van Dr. M.H.M. Heemskerk en Prof. Dr. J.H.F. Falkenburg. Tijdens deze periode werd intensief samengewerkt met de massaspectrometriegroep (Dr. P.A. van Veelen) van de afdeling Immunohematologie en Bloedtransfusie. Vanaf september 2012 is hij werkzaam als post-doctoraal onderzoeker op de afdeling Hematopoiese van Sanquin Research in Amsterdam. Hier werkt hij aan het karakteriseren van primaire T-cellen uit humaan longweefsel. Curriculum vitae 181
5 List of publications Hombrink P, Hadrup SR, Bakker A, Kester MG, Falkenburg JH, von dem Borne PA, Schumacher TN, Heemskerk MH. High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening: feasibility and limitations. PLOS One 2011;6(8):e Hombrink P, Hassan C, Kester MG, de Ru AH, van Bergen CA, Nijveen H, Drijfhout JW, Falkenburg JH, Heemskerk MH, van Veelen PA. Discovery of T cell epitopes implementing HLA-peptidomics into a reverse immunology approach. Journal of Immunology 2013 Apr 15;190(8): Hombrink P, Raz Y, Kester MG, de Boer R, Weißbrich B, von dem Borne PA, Busch DH, Schumacher TN, Falkenburg JH, Heemskerk MH. Mixed functional characteristics correlating with TCR-ligand koff -rate of MHC-tetramer reactive T cells within the naive T-cell repertoire. European Journal of Immunology 2013 Nov;43(11): Hombrink P, Hassan C, Kester MG, Jahn L, Pont MJ, Ru AH, Bergen CAM, Griffioen M, Falkenburg JH, van Veelen PA, Heemskerk MH. Identification of biological relevant minor histocompatibility antigens within the B-lymphocyte derived HLA-ligandome using a reverse immunology approach. Submitted. Publications not in this thesis Hombrink P, Backer RA, Piet B, Jongejan A, Jonkers RE, Helbig C, Amsen D, Moerland PD, van Lier RA. The transcriptional profile of human CD8 + lung resident memory T-cells. Submitted. Jahn L, Hombrink P, Hassan C, Kester MG, van der Steen DM, Hagedoorn RS, Falkenburg JH, van Veelen PA, Heemskerk MH. Therapeutic targeting of the BCR associated protein CD79b in a TCR-based approach is hampered by aberrant expression of CD79b. Submitted. van Aalderen MC, Remmerswaal EBM, Verstegen NJM, Hombrink P, ten Brinke A, Pircher H, Kootstra NA, ten Berge IJM, van Lier RA. Two dimensions in human CD8+ T-cell development: cell surface phenotype in conjunction with T-bet and Eomes expression levels predicts the functional potential of antigen-experienced CD8+ T-cells. Submitted. Linnemann C, Heemskerk B, Kvistborg P, Kluin RJ, Bolotin DA, Chen X, Bresser K, Nieuwland M, Schotte R, Michels S, Gomez-Eerland R, Jahn L, Hombrink P, Legrand N, Shu 182
6 CJ, Mamedov IZ, Velds A, Blank CU, Haanen JB, Turchaninova MA, Kerkhoven RM, Spits H, Hadrup SR, Heemskerk MH, Blankenstein T, Chudakov DM, Bendle GM, Schumacher TN. High-throughput identification of antigen-specific TCRs by TCR gene capture. Nature Medicine 2013 Nov;19(11): Hassan C, Kester MG, de Ru AH, Hombrink P, Drijfhout JW, Nijveen H, Leunissen JA, Heemskerk MH, Falkenburg JH, van Veelen PA. The human leukocyte antigen-presented ligandome of B lymphocytes. Molecular and Cellular Proteomics 2013 Jul;12(7): Falkenburg WJ, Melenhorst JJ, van de Meent M, Kester MG, Hombrink P, Heemskerk MH, Hagedoorn RS, Gostick E, Price DA, Falkenburg JH, Barrett AJ, Jedema I. Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity. Journal of Immunology 2011 Sep 1;187(5): de Jong H, Berlo SE, Hombrink P, Otten HG, van Eden W, Lafeber FP, Heurkens AH, Bijlsma JW, Glant TT, Prakken BJ. Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis. Annals of Rheumatic Diseases 2010 Jan;69(1): Hadrup SR, Bakker AH, Shu CJ, Andersen RS, van Veluw J, Hombrink P, Castermans E, Thor Straten P, Blank C, Haanen JB, Heemskerk MH, Schumacher TN. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nature Methods 2009 Jul;6(7): List of publications 183
Cover Page. The handle http://hdl.handle.net/1887/35349 holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/35349 holds various files of this Leiden University dissertation. Author: Hassan, Chopie Title: New strategies in identification and quantification of minor
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Cover Page The handle http://hdl.handle.net/1887/23080 holds various files of this Leiden University dissertation. Author: Commandeur, Susanna Title: Facing the phases of Mycobacterium tuberculosis : hunting
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Cover Page The handle http://hdl.handle.net/1887/22866 holds various files of this Leiden University dissertation. Author: Voorthuis, Alexandra Title: Future parents : childhood experiences, oxytocin and
Nadere informatiePublications PUBLICATIONS
Publications 164 Publications PUBLICATIONS 1. Heemskerk B, Veltrop-Duits LA, van Vreeswijk T, ten Dam MM, Heidt S, Toes RE, van Tol MJ, Schilham MW. Extensive cross-reactivity of CD4 + adenovirus-specific
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Cover Page The handle http://hdl.handle.net/1887/22989 holds various files of this Leiden University dissertation Author: Pouw, Lucinda Title: Emotion regulation in children with Autism Spectrum Disorder
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Cover Page The handle http://hdl.handle.net/1887/20183 holds various files of this Leiden University dissertation. Author: Rooden, Stephanie Maria van Title: Clinical patterns in Parkinson s disease Date:
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Cover Page The handle http://hdl.handle.net/1887/20154 holds various files of this Leiden University dissertation. Author: Joosen, Katharina Jacomina Title: Harsh discipline in toddlerhood. A longitudinal
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Cover Page The handle http://hdl.handle.net// holds various files of this Leiden University dissertation. Author: Verbiest, Marjolein Elisabeth Anna Title: The implementation of smoking cessation care
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Cover Page The handle http://hdl.handle.net/1887/36475 holds various files of this Leiden University dissertation. Author: Windhorst, Dina Aafje (Dafna) Title: Differential susceptibility to parenting
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Cover Page The handle http://hdl.handle.net/1887/24307 holds various files of this Leiden University dissertation Author: Broek, Colette van den Title: Optimisation of colorectal cancer treatment Issue
Nadere informatieCover Page. Author: Heijden, Thomas van der Title: The interplay between lipids and the immune system in atherosclerosis Date:
Cover Page The handle http://hdl.handle.net/1887/58107 holds various files of this Leiden University dissertation Author: Heijden, Thomas van der Title: The interplay between lipids and the immune system
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Cover Page The handle http://hdl.handle.net/1887/22212 holds various files of this Leiden University dissertation. Author: Wilde, Adriaan Hugo de Title: Host factors in nidovirus replication Issue Date:
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Cover Page The handle http://hdl.handle.net/1887/74052 holds various files of this Leiden University dissertation. Author: Winder, J.Y. Title: The UHDRS and UHDRS-FAP assessments in Huntington's disease
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Cover Page The handle http://hdl.handle.net/1887/39413 holds various files of this Leiden University dissertation Author: Reedeker, Nanda Title: Neuropsychiatric phenomena in Huntington s disease Issue
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Cover Page The handle http://hdl.handle.net/1887/45043 holds various files of this Leiden University dissertation. Author: Plak, R.D. Title: What works for whom? Differential genetic effects of early literacy
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Cover Page The handle http://hdl.handle.net/1887/57383 holds various files of this Leiden University dissertation Author: Meijer, Eline Title: This is [not] who I am : understanding identity in continued
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Cover Page The handle http://hdl.handle.net/1887/32035 holds various files of this Leiden University dissertation Author: Kleijwegt, Fleur Title: Immune regulation in type 1 diabetes : towards a tissue
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Cover Page The handle http://hdl.handle.net/1887/37530 holds various files of this Leiden University dissertation. Author: Nielen, Thijs Martinus Johannes Title: Aliteracy : causes and solutions Issue
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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
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Cover Page The handle http://hdl.handle.net/1887/44387 holds various files of this Leiden University dissertation. Author: Staveren, M.C. van Title: DPD screening to prevent toxicity in fluoropyrimidine
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