Heck, Albert J R

Meiring, Hugo D

van Els, Cécile A C M

van Veelen, Peter A

Utrecht University Repository

EDITORIALRemembering Ad de JongCécile A. C. M. van Els1, Peter A. van Veelen2, Albert J. R. Heck3, and Hugo D. Meiring4It is with great sadness that we learned of the passing awayof Ad P.J.M. de Jong, retired Principal Scientist at the NationalInstitute for Public Health and the Environment (RIVM) and theNational Vaccine Institute, both in Bilthoven (NL), in January,at the age of 75 years. Most Mass Spectrometrists do knowhim as a scientist who pioneered Biomolecular Mass Spec-trometry already in the early 1990s, with a strong focus ondeveloping nanoscale Liquid Chromatography. Many researchgroups have copied his nanoscale LC design, essentiallybased on the “Deans switching system,” which is still used inmany research institutes worldwide (1). He had many collab-orators in a large number of research groups. Together withimmunologist Cécile van Els (from RIVM and Utrecht Univer-sity, NL), he was a frontrunner in the field of ImmunoProteo-mics and ImmunoPeptidomics (2–4).Although his father and mother wished a career in farmingfor him, Ad was trained as a chemical scientist at the Uni-versity of Technology (Eindhoven, NL). He had a creative mindand was driven by curiosity and passion for his work. In 1977,he was appointed as Department Head of the Laboratory ofMass Spectrometry at the Vrije Universiteit (Amsterdam, NL)where he obtained his PhD degree in clinical chemistry in1988. As Department Head of Molecular Spectroscopy at theLaboratory of Organic Analytical Chemistry at RIVM (Bilt-hoven, Netherlands), he worked on developing and applyingMS-based techniques in environmental applications (with astrong focus on dioxin pollution in milk). He was always eagerto take up something new and challenging. In the mid-1990s,immunologists in the Vaccines Sector of his institute reachedout with an immunological project. They wanted to discoverpathogen-derived peptides that are presented in so-calledMajor Histocompatibility Complex (MHC) molecules on cellsduring infections. Such peptide–MHC complexes can trigger Tcell–mediated immune responses in fighting viral or bacterialinfections. To learn the latest in analytical chemistry in thisresearch field, Ad and one of his group members Jan tenHove, went to Donald Hunt at the University of Virginia (USA),who had pioneered nanoscale LC Electrospray Ionization MSfor the identification of T cell epitopes and laid down thefoundation of the field of ImmunoProteomics/Peptidomics. Asan early adopter of Don’s method, Ad was one of the first tosuccessfully identify non-self viral or bacterial epitopes onantigen presenting cells, typically present at sub-femtomolarFrom the 1Center for Infectious Disease Control, National Institute for PubProteomics and Metabolomics, Leiden University Medical Center, Leomics, Utrecht University, Utrecht, The Netherlands; 4Intravacc, Biltho© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for BioThis is an open access article under the CC BY license (http://creativecommons.org/licerange in peptide eluates from billions of cultured cells.Because of the analytical challenge to identify low abundantpeptide species in chemically highly similar MHC–derivedpeptide mixtures, Ad kept thinking out of the box anddesigned novel separation systems. To tease these peptidesapart prior to their MS analysis, he invented miniaturizedseparation strategies, using new types of offline and onlinefractionation strategies, employing columns of dazzlinglengths (≥200 cm), miniaturized diameters (down to 25 μm),and mixed-bed or multi-bed stationary phases already in themid-1990s (5–7). “We could always find him with a big smilesitting behind a Mass Spectrometer rather than behind hisoffice desk, until the late/early hours, testing one of his newideas on nanoscale LC-MS for better performance,” immu-nologist and close colleague Cécile van Els remembers.Friend and colleague Peter van Veelen from Leiden UniversityMedical Centre (Leiden, NL), who still saw him biweekly tocook and play chess together, adds: “Ad has been pioneering,teaching and spreading nanoscale LC and ImmunoProteo-mics/Peptidomics avant lettre in the Netherlands and farbeyond”. This was also the trigger for him to start Nano-Separations, one of the first commercial companies world-wide, providing a portfolio on tailor-made solutions andsupport on nanoscale separation systems with a focus onbiomolecular MS-based applications. With new generations ofMS instruments coming on the market, gaining higher sensi-tivity, resolution, and acquisition, speed in ImmunoProteo-mics/Peptidomics seemed evident, but it was not. Without histailor-made 2D pre-fractionation and nanoscale LC separa-tion, undersampling masked the rare epitopes of interest. Adwas very instrumental. Albert Heck (Utrecht University, NL)recalls the many demo activities with Ad when going for in-vestments in new mass spectrometers to the demo sites ofthe manufacturers: “We did always try to bring, to my greatpleasure, Ad and his nanoscale LC system with us. His sep-aration system by far outperformed those available in thedemo labs. After such demos, manufacturers often asked ifthey could keep Ad’s nanoscale LC system, to revisit their“failed” demos of the last couple of months and Ad also hel-ped them”. Ad always kept helping people, with his love fornanoscale LC, mass spectrometry, and immunoproteomics/peptidomics. Heck also remembers his very clever use ofstable isotopically labeled pathogens to unambiguouslylic Health and the Environment, Bilthoven, The Netherlands; 2Center foriden, The Netherlands; 3Biomolecular Mass Spectrometry and Prote-ven, The NetherlandsMol Cell Proteomics (2023) 22(6) 100568 1chemistry and Molecular Biology.nses/by/4.0/). https://doi.org/10.1016/j.mcpro.2023.100568FIG. 1. Ad de Jong in 2005.Remembering Ad de Jongdiscriminate between pathogenic-derived HLA peptides fromself-peptides, a few years even before SILAC was born (8).“Ad was a very creative scientist and should be credited forquite a few inventions in our field, but he always liked to stayout of the spotlights and, frankly, I believe he did not like towrite and publish” Albert recalls. Part of the technical de-velopments and improvements were performed during his 6-months sabbatical leave in the early 2000s, that he spent atthe Matthias Mann group at the University of SouthernDenmark (Odense, DK). Together with Hugo Meiring, his rightand “validating” hand in the group, Ad visited other (Immuno)Proteomics groups or Mass Spectrometer developersthroughout Europe to exchange knowledge and plug in andplay their nanoseparation system, always demonstrating su-perior performance.Ad was a modest scientist, claiming little fame in his field.He was driven by his passion for mass spectrometry and byinventiveness, always chasing freedom and autonomy in hiswork. He kept his focus on pathogen-related proteomics2 Mol Cell Proteomics (2023) 22(6) 100568analyses in vaccinology. Nowadays, the ImmunoProteomics/Peptidomics field has grown and moved into the elucidation ofneoepitopes in cancer. Directly or indirectly, Ad did inspiremany of these groups through his nanoscale-LC approach inMass Spectrometric analysis of ImmunoPeptidomes.Ad was married to Jeanne Beenackers, an autodidactartist and the love of his life. They got two daughters,Charlotte and Marloes, and two grandchildren, Anna andMax. They all loved the beauty of nature, in particular,rugged mountain regions and the sea: always enjoyinghiking, bicycling, and sailing. Unfortunately, Jeanne passedaway already in 2012 and in this same period, Ad devel-oped cancer. This, all, coincided with his retirement. Missingboth his beloved wife and work felt heavy on him. He neverregained his good health. Nevertheless, he enjoyed beingwith family and good friends, as well as stimulating culturein his municipality and organizing art exhibitions of Jeanne’swork for many years, until he passed away at home onJanuary 22, 2023. He will be dearly missed (Fig. 1).REFERENCES1. Meiring, H. D., van der Heeft, E., ten Hove, G. J., and de Jong, A. P. J. M.(2002) Nanoscale LC-MS(n): technical design and applications to peptideand protein analysis. J. Sep. Sci. 25, 557–5682. de Jong, A. (1998) Contribution of mass spectrometry to contemporaryimmunology. Mass Spectrom. Rev. 17, 311–3353. van der Heeft, E., ten Hove, G. J., Herberts, C. A., Meiring, H. D., van Els, C.A., and de Jong, A. P. (1998) A microcapillary column switching HPLC-electrospray ionization MS system for the direct identification of pep-tides presented by major histocompatibility complex class I molecules.Anal. Chem. 70, 3742–37514. van Els, C. A., Herberts, C. A., van der Heeft, E., Poelen, M. C., van Gaans-van den Brink, J. A., van der Kooi, A., et al. (2000) A single naturally pro-cessed measles virus peptide fully dominates the HLA-A*0201-associatedpeptide display and is mutated at its anchor position in persistent viralstrains. Eur. J. Immunol. 30, 1172–11815. Mommen, G. P., Meiring, H. D., Heck, A. J., and de Jong, A. P. (2013) Mixed-bed ion exchange chromatography employing a salt-free pH gradient forimproved sensitivity and compatibility in MudPIT. Anal. Chem. 85, 6608–66166. Mommen, G. P., van de Waterbeemd, B., Meiring, H. D., Kersten, G., Heck,A. J., and de Jong, A. P. (2012) Unbiased selective isolation of protein N-terminal peptides from complex proteome samples using phospho tagging(PTAG) and TiO(2)-based depletion. Mol. Cell. Proteomics 11, 832–8427. Mommen, G. P., Frese, C. K., Meiring, H. D., van Gaans-van den Brink, J., deJong, A. P., van Els, C. A., et al. (2014) Expanding the detectable HLApeptide repertoire using electron-transfer/higher-energy collision dissoci-ation (EThcD). Proc. Natl. Acad. Sci. U. S. A. 111, 4507–45128. Meiring, H. D., Soethout, E. C., Poelen, M. C., Mooibroek, D., Hoogerbrugge,R., Timmermans, H., et al. (2006) Stable isotope tagging of epitopes: ahighly selective strategy for the identification of major histocompatibilitycomplex class I-associated peptides induced upon viral infection. Mol.Cell. Proteomics 5, 902–913

Remembering Ad de Jong

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Remembering Ad de Jong

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