Mass spectrometry-based proteomics has become an invaluable tool in modern biomedical research. The proteomics group performs state-of-the art mass spectrometric analyses of peptides/proteins, with an historical focus on immunology, i.e. HLA-peptidomics, cell biology and microbiology. Our primary focus is on method development to improve the depth of identification of proteomes and peptidomes to enable a better understanding of mechanisms in health and disease. Also, we use these methodologies to elucidate protein function e.g. of proteases. To this end, a wide variety of chromatographic (C18, SCX, AEX, HILIC, TiO2, affinity chromatography) and electrophoretic (SDS-PAGE, CE, IEF) techniques is available. The available mass spectrometric equipment comprises a Q-Exactive, LTQ-FT Ultra, several amaZon ion traps -including ETD-, and an UltrafleXtreme.

Standard analyses/techniques we apply include:
  • Proteomics and (HLA)-Peptidomics
  • Relative protein quantification (SILAC, Dimethyl labelling)
  • Identification of post-translational modifications (e.g. deamidation, citrullination, phosphorylation)
  • Quantitation by MRM/PRM


Highlights of our research
  • The elucidation of two new enzymes, nardilysin and TOP, shown to be involved in antigen processing, i.e. in the creation of epitopes/HLA-ligands. This finding adds an extra level of complexity to antigen processing.
  • The role of miRNAs in the development of lymphocytes and their relevance to the development of acute myeloid leukemia (AML), with Dept. Hematology of the Erasmus MC in Rotterdam.
  • The elucidation of various T cell epitopes relevant to celiac disease, cancer, diabetes and transplantation.
  • Elucidation by a peptidomics approach of minor histocompatibility antigens relevant to the treatment of leukemia (with the Dept. Hematology).
  • The role of post-translational modifications in Rheuma, in particular of carbamylation.
  • Identification of novel glycoforms of apolipoprotein CIII and analysis of the corresponding glycopeptides in urine of S. mansoni-infected individuals
  • The elucidation of a novel proline specific metalloprotease in C. difficile involved in adhesion (with Dept. Medical Microbiology)
  • Unraveling of the unique substrate specificity of the C. difficile sortase (with Dept. Medical Microbiology)
  • Elucidation of novel glycoforms of fibrinogen α-chain and analysis of the corresponding glycopeptides in patients with urinary tract infections


Financial support

Netherlands Organisation for Scientific Research (NWO), Landsteiner Foundation for Blood Transfusion Research (LSBR), National Institute of Health and the Environment (RIVM) the Netherlands Proteomics Centre (NPC), Dutch Cancer Society (KWF) and the LUMC.


Currently we have collaborations with many groups within the LUMC (e.g. IHB, Hematology, Rheumatology, Clinical Oncology, Molecular Cell Biology, Toxicogenetics, Human Genetics, Pathology, Infectious Diseases, Medical Microbiology) but also with research groups from other universities and research institutes, e.g. NKI, RIVM, in the Netherlands and abroad. In addition, we collaborate with industrial partners.


Dr. Peter van Veelen
Phone: +31 71 5264656


Dr. Paul J. Hensbergen
Dr. George Janssen
Arnoud de Ru
Ing. Irina Dragan
Drs. Jeroen de Keijzer
Frank Fleurbaaij, Msc.

Selected publications

Alemdehy MF, Haanstra JR, de Looper HW, van Strien PM, Verhagen-Oldenampsen J, Caljouw Y, Sanders MA, Hoogenboezem R, de Ru AH, Janssen GM, Smetsers SE,Bierings MB, van Veelen PA, von Lindern M, Touw IP, Erkeland SJ. ICL-inducedmiR139-3p and miR199a-3p have opposite roles in hematopoietic cell expansion and leukemic transformation. Blood. 2015 Jun 18;125(25):3937-48. doi:10.1182/blood-2014-11-612507. Epub 2015 Mar 16. PubMed PMID: 25778535.

Treffers EE, Tas A, Scholte FE, Van MN, Heemskerk MT, de Ru AH, Snijder EJ,van Hemert MJ, van Veelen PA. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication. Proteomics. 2015 Jul;15(13):2267-80. doi: 10.1002/pmic.201400581. Epub 2015 Apr 22. PubMed PMID: 25764339.

Garstka MA, Fish A, Celie PH, Joosten RP, Janssen GM, Berlin I, Hoppes R, Stadnik M, Janssen L, Ovaa H, van Veelen PA, Perrakis A, Neefjes J. The first step of peptide selection in antigen presentation by MHC class I molecules. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1505-10. doi: 10.1073/pnas.1416543112. Epub 2015 Jan 20. PubMed PMID: 25605945; PubMed Central PMCID: PMC4321303.

Hombrink P, Hassan C, Kester MG, Jahn L, Pont MJ, de Ru AH, van Bergen CA, 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. Clin Cancer Res. 2015 May 1;21(9):2177-86. doi: 10.1158/1078-0432.CCR-14-2188. Epub2015 Jan 14. PubMed PMID: 25589627.

Hassan C, Chabrol E, Jahn L, Kester MG, de Ru AH, Drijfhout JW, Rossjohn J, Falkenburg JH, Heemskerk MH, Gras S, van Veelen PA. Naturally processed non-canonical HLA-A*02:01 presented peptides. J Biol Chem. 2015 Jan 30;290(5):2593-603. doi: 10.1074/jbc.M114.607028. Epub 2014 Dec 12. PubMed PMID: 25505266; PubMed Central PMCID: PMC4317018.

van Leeuwen HC, Klychnikov OI, Menks MA, Kuijper EJ, Drijfhout JW, Hensbergen PJ. Clostridium difficile sortase recognizes a (S/P)PXTG sequence motif and can accommodate diaminopimelic acid as a substrate for transpeptidation. FEBS Lett. 2014 Nov 28;588(23):4325-33. doi: 10.1016/j.febslet.2014.09.041. Epub 2014 Oct 23. PubMed PMID: 25305382.

Fleurbaaij F, Heemskerk AA, Russcher A, Klychnikov OI, Deelder AM, Mayboroda OA, Kuijper EJ, van Leeuwen HC, Hensbergen PJ. Capillary-electrophoresis mass spectrometry for the detection of carbapenemases in (multi-)drug-resistant Gram-negative bacteria. Anal Chem. 2014 Sep 16;86(18):9154-61. doi: 10.1021/ac502049p. Epub 2014 Sep 4. PubMed PMID: 25155175.

Hassan C, Kester MG, Oudgenoeg G, de Ru AH, Janssen GM, Drijfhout JW, Spaapen RM, Jiménez CR, Heemskerk MH, Falkenburg JH, van Veelen PA. Accurate quantitation of MHC-bound peptides by application of isotopically labeled peptide MHC complexes. J Proteomics. 2014 Sep 23;109:240-4. doi: 10.1016/j.jprot.2014.07.009.Epub 2014 Jul 19. PubMed PMID: 25050860.

de Keijzer J, de Haas PE, de Ru AH, van Veelen PA, van Soolingen D. Disclosure of selective advantages in the “modern” sublineage of the Mycobacterium tuberculosis Beijing genotype family by quantitative proteomics. Mol Cell Proteomics. 2014 Oct;13(10):2632-45. doi: 10.1074/mcp.M114.038380. Epub 2014 Jul 14. PubMed PMID: 25022876; PubMed Central PMCID: PMC4188992.

Li Y, Treffers EE, Napthine S, Tas A, Zhu L, Sun Z, Bell S, Mark BL, van Veelen PA, van Hemert MJ, Firth AE, Brierley I, Snijder EJ, Fang Y. Transactivation of programmed ribosomal frameshifting by a viral protein. Proc Natl Acad Sci U S A. 2014 May 27;111(21):E2172-81. doi: 10.1073/pnas.1321930111. Epub 2014 May 13. PubMed PMID: 24825891; PubMed Central PMCID: PMC4040542.

Hensbergen PJ, Klychnikov OI, Bakker D, van Winden VJ, Ras N, Kemp AC, Cordfunke RA, Dragan I, Deelder AM, Kuijper EJ, Corver J, Drijfhout JW, van Leeuwen HC. A novel secreted metalloprotease (CD2830) from Clostridium difficile cleaves specific proline sequences in LPXTG cell surface proteins. Mol Cell Proteomics. 2014 May;13(5):1231-44. doi: 10.1074/mcp.M113.034728. Epub 2014 Mar 12. PubMed PMID: 24623589; PubMed Central PMCID: PMC4014281.

van der Plas MJ, Andersen AS, Nazir S, van Tilburg NH, Oestergaard PR, Krogfelt KA, van Dissel JT, Hensbergen PJ, Bertina RM, Nibbering PH. A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis. PLoS One. 2014 Mar 19;9(3):e92096. doi: 10.1371/journal.pone.0092096. eCollection 2014. Erratum in: PLoS One. 2014;9(6):e101646. PubMed PMID: 24647546; PubMed Central PMCID: PMC3960166.

van Lummel M, Duinkerken G, van Veelen PA, de Ru A, Cordfunke R, Zaldumbide A, Gomez-Touriño I, Arif S, Peakman M, Drijfhout JW, Roep BO. Posttranslational modification of HLA-DQ binding islet autoantigens in type 1 diabetes. Diabetes. 2014 Jan;63(1):237-47. doi: 10.2337/db12-1214. Epub 2013 Oct 2. PubMed PMID: 24089515.

Nicolardi S, van der Burgt YE, Dragan I, Hensbergen PJ, Deelder AM. Identification of new apolipoprotein-CIII glycoforms with ultrahigh resolution MALDI-FTICR mass spectrometry of human sera. J Proteome Res. 2013 May 3;12(5):2260-8. doi: 10.1021/pr400136p. Epub 2013 Apr 5. PubMed PMID: 23527852.

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. Mol Cell Proteomics. 2013 Jul;12(7):1829-43. doi: 10.1074/mcp.M112.024810. Epub 2013 Mar 12. PubMed PMID: 23481700; PubMed Central PMCID: PMC3708169.

Zauner G, Hoffmann M, Rapp E, Koeleman CA, Dragan I, Deelder AM, Wuhrer M, Hensbergen PJ. Glycoproteomic analysis of human fibrinogen reveals novel regions  of O-glycosylation. J Proteome Res. 2012 Dec 7;11(12):5804-14. doi: 10.1021/pr3005937. Epub 2012 Oct 29. PubMed PMID: 23050552.

van der Does AM, Hensbergen PJ, Bogaards SJ, Cansoy M, Deelder AM, van Leeuwen HC, Drijfhout JW, van Dissel JT, Nibbering PH. The human lactoferrin-derived peptide hLF1-11 exerts immunomodulatory effects by specific inhibition of myeloperoxidase activity. J Immunol. 2012 May 15;188(10):5012-9. doi: 10.4049/jimmunol.1102777. Epub 2012 Apr 20. PubMed PMID: 22523385.

Kronenberg D, Knight RR, Estorninho M, Ellis RJ, Kester MG, de Ru A, Eichmann M, Huang GC, Powrie J, Dayan CM, Skowera A, van Veelen PA, Peakman M. Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill β-cells. Diabetes. 2012 Jul;61(7):1752-9. doi: 10.2337/db11-1520. Epub 2012 Apr 20. PubMed PMID: 22522618; PubMed Central PMCID: PMC3379678.

Pacchiarotta T, Hensbergen PJ, Wuhrer M, van Nieuwkoop C, Nevedomskaya E, Derks RJ, Schoenmaker B, Koeleman CA, van Dissel J, Deelder AM, Mayboroda OA. Fibrinogen alpha chain O-glycopeptides as possible markers of urinary tract infection. J Proteomics. 2012 Jan 4;75(3):1067-73. doi: 10.1016/j.jprot.2011.10.021. Epub 2011 Oct 31. PubMed PMID: 22075168.

Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GM, van Veelen PA, Levarht NE, van der Helm-van Mil AH, Cerami A, Huizinga TW, Toes RE, Trouw LA. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17372-7. doi: 10.1073/pnas.1114465108. Epub 2011 Oct 10. PubMed PMID: 21987802; PubMed Central PMCID: PMC3198314.

Amir AL, van der Steen DM, Hagedoorn RS, Kester MG, van Bergen CA, Drijfhout JW, de Ru AH, Falkenburg JH, van Veelen PA, Heemskerk MH. Allo-HLA-reactive T cells inducing graft-versus-host disease are single peptide specific. Blood. 2011 Dec 22;118(26):6733-42. doi: 10.1182/blood-2011-05-354787. Epub 2011 Oct 4. PubMed PMID: 21972290.

Selected publications

Kessler JH, Khan S, Seifert U, Le Gall S, Chow KM, Paschen A, Bres-Vloemans SA, de Ru A, van Montfoort N, Franken KL, Benckhuijsen WE, Brooks JM, van Hall T, Ray K, Mulder A, Doxiadis II, van Swieten PF, Overkleeft HS, Prat A, Tomkinson B, Neefjes J, Kloetzel PM, Rodgers DW, Hersh LB, Drijfhout JW, van Veelen PA, Ossendorp F, Melief CJ. Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes. Nat Immunol. 2011 Jan;12(1):45-53. doi: 10.1038/ni.1974. Epub 2010 Dec 12. PubMed PMID: 21151101.

Balog CI, Mayboroda OA, Wuhrer M, Hokke CH, Deelder AM, Hensbergen PJ. Mass spectrometric identification of aberrantly glycosylated human apolipoprotein C-III peptides in urine from Schistosoma mansoni-infected individuals. Mol Cell Proteomics. 2010 Apr;9(4):667-81. doi: 10.1074/mcp.M900537-MCP200. Epub 2010 Jan 13. PubMed PMID: 20071361; PubMed Central PMCID: PMC2860228.

Oliveira CC, van Veelen PA, Querido B, de Ru A, Sluijter M, Laban S, Drijfhout JW, van der Burg SH, Offringa R, van Hall T. The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects. J Exp Med. 2010 Jan 18;207(1):207-21. doi: 10.1084/jem.20091429. Epub 2009 Dec 28. Erratum in: J Exp Med. 2010 Mar 15;207(3):671. Drijfhout, Jan W [added]. PubMed PMID: 20038604; PubMed Central PMCID: PMC2812552.

Stepniak D, Wiesner M, de Ru AH, Moustakas AK, Drijfhout JW, Papadopoulos GK, van Veelen PA, Koning F. Large-scale characterization of natural ligands explains the unique gluten-binding properties of HLA-DQ2. J Immunol. 2008 Mar 1;180(5):3268-78. PubMed PMID: 18292551.

Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, Camphausen K, Luiten RM, de Ru AH, Neijssen J, Griekspoor A, Mesman E, Verreck FA, Spits H, Schlom J, van Veelen P, Neefjes JJ. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006 May 15;203(5):1259-71. Epub 2006 Apr 24. PubMed PMID: 16636135; PubMed Central PMCID: PMC3212727.

van de Wal Y, Kooy YM, van Veelen PA, Peña SA, Mearin LM, Molberg O, Lundin KE, Sollid LM, Mutis T,  enckhuijsen WE, Drijfhout JW, Koning F. Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10050-4. PubMed PMID: 9707598; PubMed Central PMCID: PMC21459.