Article
Ophthalmology
Sahar Gelfman, Dominique Monnet, Ann J. Ligocki, Thierry Tabary, Arden Moscati, Xiaodong Bai, Jan Freudenberg, Blerta Cooper, Jack A. Kosmicki, Sarah Wolf, Manuel A. R. Ferreira, John Overton, Jonathan Weyne, Eli A. Stahl, Aris Baras, Carmelo Romano, Jacques H. M. Cohen, Giovanni Coppola, Antoine Brezin
Summary: This study identified that carrying a second allele from the HLA-Aw19 broad antigen family increases the risk for Birdshot chorioretinopathy (BSCR) and that ERAP1 and ERAP2 haplotypes modulate disease risk. A combination of ERAP1/ERAP2 risk genotypes with two copies of HLA-Aw19 alleles further increases the risk of BSCR.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Immunology
W. J. Venema, S. Hiddingh, G. M. C. Janssen, J. Ossewaarde-van Norel, N. Dam van Loon, J. H. de Boer, P. A. van Veelen, J. J. W. Kuiper
Summary: This study identified the naturally presented antigenic SAG peptides through HLA-A29 immunopeptidomics and found that SAG is not a CD8+ T cell autoantigen, suggesting that it is not involved in the pathogenesis of BCR.
CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Georges Bedran, Daniel A. Polasky, Yi Hsiao, Fengchao Yu, Felipe da Veiga Leprevost, Javier A. Alfaro, Marcin Cieslik, Alexey I. Nesvizhskii
Summary: In this study, a fast computational workflow merging the MSFragger-Glyco search algorithm with a false discovery rate control is introduced for analyzing glycopeptides from mass spectrometry-based immunopeptidome data. The authors analyze eight large-scale publicly available studies and find that glycosylated MHC-associated peptides are predominantly presented by MHC class II. They present a comprehensive resource, HLA-Glyco, which contains over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights into glycosylation properties in antigen recognition and immune modulation.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Hematology
Juliane Sarah
Summary: Permissive HLA-DPB1 mismatches have more overlap in HLA-presented peptide repertoire, leading to lower frequency and diversity of alloreactive TCRb clonotypes, which can be reversed by silencing of the peptide editor HLA-DM.
Article
Medicine, General & Internal
Marina Papadia, Carlos Pavesio, Christine Fardeau, Piergiorgio Neri, Philippe Kestelyn, Ioannis Papasavvas, Carl P. Herbort
Summary: The appraisal of HLA-A29 birdshot retinochoroiditis (BRC) has improved through advances in investigational methods, leading to better understanding and management of the disease. Essential factors for better appraisal and understanding include new immunopathological hypotheses, the importance of HLA testing, crucial imaging modalities, early diagnostic criteria, and the need for early aggressive treatment with multiple immunosuppressive agents.
Article
Hematology
Thuja Meurer, Pietro Crivello, Maximilian Metzing, Michel Kester, Dominik A. Megger, Weiqiang Chen, Peter A. van Veelen, Peter van Balen, Astrid M. Westendorf, Georg Homa, Sophia E. Layer, Amin T. Turki, Marieke Griffioen, Peter A. Horn, Barbara Sitek, Dietrich W. Beelen, J. H. Frederik Falkenburg, Esteban Arrieta-Bolanos, Katharina Fleischhauer
Summary: Research revealed that permissive HLA-DPB1 mismatches in hematopoietic cell transplantation have higher peptide repertoire overlaps and lower frequency and diversity of alloreactive TCR beta clonotypes in healthy individuals and transplanted patients compared to nonpermissive mismatches. The permissiveness can be reversed by peptide editor HLA-DM or its antagonist, HLA-DO, through significant broadening of the peptide repertoire. This highlights the key role of HLA-DM in harnessing T-cell alloreactivity to HLA-DP, making it a potential novel target for cellular and immunotherapy of leukemia.
Article
Biochemical Research Methods
Putty-Reddy Sudhir, Tai-Du Lin, Qibin Zhang
Summary: This study conducted HLA allele-specific quantitative immunopeptidomics using B lymphocytes from T1D patients and healthy controls, revealing hundreds of immunopeptides differentially regulated in T1D per HLA allele. These findings may aid in better understanding HLA allele-specific antigen presentation and identifying immunopeptides for therapeutic applications in autoimmune diseases.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Ophthalmology
Edmund Tsui, Jaskirat S. Takhar, Ashlin Joye, Tessnim R. Ahmad, Nisha R. Acharya, John A. Gonzales
Summary: This study describes high-resolution DNA typing of HLA-A29 in two families with familial birdshot chorioretinopathy (BSCR), including clinical outcomes of multigenerational BSCR, with positive results for the HLA-A29*02 allele in all affected individuals.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2021)
Article
Biology
Jonas Birkelund Nilsson, Saghar Kaabinejadian, Hooman Yari, Bjoern Peters, Carolina Barra, Loren Gragert, William Hildebrand, Morten Nielsen
Summary: This study addresses the prediction of HLA-DQ antigen presentation and the contribution of trans-only variants in shaping the HLA-DQ immunopeptidome. By integrating immunoinformatics data mining models with mass spectrometry immunopeptidomics data, the study demonstrates improved predictive power and molecular coverage for models trained with novel HLA-DQ data. The study also reveals the limited contribution of trans-only HLA-DQ variants to the overall HLA-DQ immunopeptidome.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Montserrat Puig, Suryatheja Ananthula, Ramesh Venna, Swamy Kumar Polumuri, Elliot Mattson, Lacey M. Walker, Marco Cardone, Mayumi Takahashi, Shan Su, Lisa F. Boyd, Kannan Natarajan, Galina Abdoulaeva, Wells W. Wu, Gregory Roderiquez, William H. Hildebrand, Serge L. Beaucage, Zhihua Li, David H. Margulies, Michael A. Norcross
Summary: The interaction between flucloxacillin (FLX) and HLA-B*57:01 may lead to the formation of neoantigens, causing severe hypersensitivity reactions. FLX treatment diversifies the immunopeptidome of cells, enriching it with drug-modified peptides that induce specific CD8(+) T cell responses. FLX-modified lysines on peptides may impact interactions with KIR or TCR, affecting NK and T cell function.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Yue A. Qi, Tapan K. Maity, Constance M. Cultraro, Vikram Misra, Xu Zhang, Catherine Ade, Shaojian Gao, David Milewski, Khoa D. Nguyen, Mohammad H. Ebrahimabadi, Ken-ichi Hanada, Javed Khan, Cenk Sahinalp, James C. Yang, Udayan Guha
Summary: The study identified potential immunogenic human leukocyte antigen (HLA) class I-presented peptides in melanoma and EGFR-mutant lung adenocarcinoma using large-scale proteogenomic profiling. This discovery could be valuable for developing precision immunotherapies.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Immunology
Ioannis Temponeras, Martina Samiotaki, Despoina Koumantou, Martha Nikopaschou, Jonas J. W. Kuiper, George Panayotou, Efstratios Stratikos
Summary: ER Aminopeptidase 1 (ERAP1) is an ER-resident aminopeptidase that plays a role in antigen presentation and may be targeted for cancer immunotherapy. In this study, researchers used an inhibitor to explore the effect of targeting ERAP1 on the immunopeptidome of a human cancer cell line. The results showed significant differences in peptide composition and HLA allele utilization between allosterically inhibited and ERAP1 KO cells, suggesting distinct roles for the allosteric regulatory site of ERAP1 in antigenic peptide selection.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar de Rojasj, Thiago Peixoto Leal, Akinori Miyashita, Celine Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Kucukali, Seth D. Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E. Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, Maria J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stephanie Debette, Jean-Francois Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo Garcia-Ribas, Jose Maria Garcia-Alberca, Pablo Garcia-Gonzalez, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonca, Merce Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Borge G. Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A. L. Pijnenburg, Gerard Pinol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puertaj Jordi Perez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M. Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A. Ross, Jose Luis Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John van Swieten, Raquel Sanchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhangc, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G. Kehoe, Ole A. Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sanchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Todau, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje van der Fliere, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D. Greicius, Emmanuel Mignot
Summary: We analyzed the HLA associations in individuals with Parkinson's disease and Alzheimer's disease across different ancestry groups and found that these two diseases share a common protective association at the HLA locus. Fine-mapping showed that specific subtypes of HLA-DRB1*04 were responsible for this association, with HLA-DRB1*04:04 and HLA-DRB1*04:07 showing the strongest association. This protective effect was also associated with decreased neurofibrillary tangles in the brain and reduced levels of tau protein in cerebrospinal fluid.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemical Research Methods
Theo Sturm, Benedikt Sautter, Tobias P. Worner, Stefan Stevanovic, Hans-Georg Rammensee, Oliver Planz, Albert J. R. Heck, Ruedi Aebersold
Summary: This study shows that an optimized mild acid elution (MAE) method can effectively isolate MHC peptide ligands with high purity, providing advantages such as the discovery of unmodified cysteine residues in MHC ligands and enabling high-confidence analysis of post-translational modifications. The results suggest that MAE could be a valuable alternative to MHC immunoaffinity chromatography (MHC-IAC) for suspension cells, offering a cost-effective solution for comprehensive and unbiased characterization of MHC peptide ligands.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Le Zhang, Geng Liu, Guixue Hou, Haitao Xiang, Xi Zhang, Ying Huang, Xiuqing Zhang, Bo Li, Leo J. Lee
Summary: This study developed a motif-guided immunopeptidome database building tool called IntroSpect to improve the sensitivity and accuracy of mass spectrometry identifications. Compared to other methods, IntroSpect does not depend on external HLA data and allows for convenient control of global FDR. Additionally, IntroSpect can be used to discover neoepitopes directly from MS data.
Article
Orthopedics
M. Tuerlings, G. M. C. Janssen, I. Boone, M. van Hoolwerff, A. Rodriguez Ruiz, E. Houtman, H. E. D. Suchiman, R. J. P. van der Wal, R. G. H. H. Nelissen, R. Coutinho de Almeida, P. A. van Veelen, Y. F. M. Ramos, I. Meulenbelt
Summary: The study aims to explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and examine the cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage. The study found 98 highly correlated genes in lesioned OA cartilage when performing Spearman correlations. Upregulation of WWP2 in 3D chondrocyte pellet cultures resulted in changes in the expression of various genes and proteins related to cartilage matrix deposition. Additionally, miR-140 was found to be involved in similar pathways as WWP2.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Immunology
W. J. Venema, S. Hiddingh, G. M. C. Janssen, J. Ossewaarde-van Norel, N. Dam van Loon, J. H. de Boer, P. A. van Veelen, J. J. W. Kuiper
Summary: This study identified the naturally presented antigenic SAG peptides through HLA-A29 immunopeptidomics and found that SAG is not a CD8+ T cell autoantigen, suggesting that it is not involved in the pathogenesis of BCR.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
K. Madunic, Y. M. C. A. Luijkx, O. A. Mayboroda, G. M. C. Janssen, P. A. van Veelen, K. Strijbis, T. Wennekes, G. S. M. Lageveen-Kammeijer, M. Wuhrer
Summary: This study identified specific mucin O-glycans that mark butyrate-induced epithelial differentiation of the intestinal cell line CaCo-2 using porous graphitized carbon nano-liquid chromatography with electrospray ionization tandem mass spectrometry. The results showed that the fully differentiated butyrate-stimulated cells have a higher expression of sialylated O-glycan structures, while fucosylation is downregulated during differentiation. These findings provide insights into the dynamic O-glycosylation patterns in the gut and their functional role in gut-microbiota homeostasis and dysbiosis.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Rheumatology
Jonas J. W. Kuiper, Joerg C. Prinz, Efstratios Stratikos, Piotr Kusnierczyk, Akiko Arakawa, Sebastian Springer, Dillon Mintoff, Ivan Padjen, Russka Shumnalieva, Secil Vural, Ina Koetter, Marleen G. van de Sande, Ayse Boyvat, Joke H. de Boer, George Bertsias, Niek de Vries, Charlotte L. M. Krieckaert, Ines Leal, Natasa Vidovic Valentincic, Ilknur Tugal-Tutkun, Hanane el Khaldi Ahanach, Felicie Costantino, Simon Glatigny, Danijela Mrazovac Zimak, Fabian Loetscher, Floor G. Kerstens, Marija Bakula, Elsa Viera Sousa, Peter Boehm, Kees Bosman, Tony J. Kenna, Simon J. Powis, Maxime Breban, Ahmet Gul, John Bowes, Rik J. U. Lories, Johannes Nowatzky, Gerrit Jan Wolbink, Dennis G. McGonagle, Franktien Turkstra
Summary: The 'MHC-I-opathy' concept describes a group of inflammatory diseases with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. However, the understanding and treatment of these disorders is limited due to patient heterogeneity and lack of systematic investigation. Therefore, interdisciplinary collaboration is needed to decipher the underlying disease mechanisms.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Ioannis Temponeras, Martina Samiotaki, Despoina Koumantou, Martha Nikopaschou, Jonas J. W. Kuiper, George Panayotou, Efstratios Stratikos
Summary: ER Aminopeptidase 1 (ERAP1) is an ER-resident aminopeptidase that plays a role in antigen presentation and may be targeted for cancer immunotherapy. In this study, researchers used an inhibitor to explore the effect of targeting ERAP1 on the immunopeptidome of a human cancer cell line. The results showed significant differences in peptide composition and HLA allele utilization between allosterically inhibited and ERAP1 KO cells, suggesting distinct roles for the allosteric regulatory site of ERAP1 in antigenic peptide selection.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Oncology
Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Martijn Kremer, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: Jchain is highly expressed in multiple myeloma (MM) and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. Using immunopeptidomics, Jchain-derived epitopes presented by MM cells were identified, and Jchain-specific T-cell clones were isolated using pHLA tetramer technology. TCRs targeting Jchain-derived peptides presented in four common HLA alleles demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Correction
Multidisciplinary Sciences
Zachary Maben, Richa Arya, Dimitris Georgiadis, Efstratios Stratikos, Lawrence J. Stern
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Bert van de Kooij, Evert de Vries, Rogier W. Rooswinkel, George M. C. Janssen, Frederique K. Kok, Peter A. van Veelen, Jannie Borst
Summary: The majority of proteins in mammalian cells are modified by N-terminal acetylation, which can have both inhibitory and promoting effects on protein degradation. However, proteome-wide stability measurements did not find a consistent correlation between N-terminal acetylation and protein stability. By analyzing protein stability datasets, it was found that N-terminal acetylation positively correlates with protein stability for GFP, but this correlation does not apply to the entire proteome. Further experiments showed that N-terminal acetylation can affect protein stability through competition with N-terminal ubiquitination, as well as other mechanisms independent of ubiquitination status.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Emmely E. E. Treffers, Ali Tas, Florine E. M. Scholte, Arnoud H. H. de Ru, Eric J. J. Snijder, Peter A. A. van Veelen, Martijn J. J. van Hemert
Summary: Chikungunya virus (CHIKV) is a reemerging alphavirus that has caused outbreaks in Africa, Asia, and the Americas. Infection with CHIKV induces phosphorylation of eukaryotic elongation factor 2 (eEF2), leading to a shut-off of host-cell translation. This shut-off is mediated by the enzymatic activity of the nsP2 NTPase domain, which increases cellular cAMP concentration and activates PKA and eEF2 kinases. These findings provide insights into how alphaviruses modulate host cell metabolism and shut-off cellular protein synthesis.
Article
Immunology
Rosa A. van Amerongen, Sander Tuit, Anne K. Wouters, Marian van de Meent, Sterre L. Siekman, Miranda H. Meeuwsen, Tassilo L. A. Wachsmann, Dennis F. G. Remst, Renate S. Hagedoorn, Dirk M. van der Steen, Arnoud H. de Ru, Els M. E. Verdegaal, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: Recurrent disease is common in ovarian cancer patients. Adoptive T-cell therapies using T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) show promise in treating less-immunogenic 'cold' ovarian tumors. This study identified PRAME, CTCFL, and CLDN6 as strictly tumor-specific TAAs with high expression in ovarian cancer and low expression in healthy tissues. High-avidity T-cell clones recognizing peptides derived from these TAAs were isolated and showed potent antitumor reactivity in vitro and in vivo. These findings provide valuable candidates for the treatment of ovarian cancer and other PRAME or CTCFL expressing cancers.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Marije A. J. de Rooij, Dennis F. G. Remst, Dirk M. van der Steen, Anne K. Wouters, Renate S. Hagedoorn, Michel G. D. Kester, Miranda H. Meeuwsen, Tassilo L. A. Wachsmann, Arnoud H. de Ru, Peter A. van Veelen, Els M. E. Verdegaal, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: In this study, high-affinity cancer-specific TCRs targeting different melanoma-associated antigens (MAGEs) were identified and tested for antitumor efficacy. The most potent TCRs were transferred into CD8+ T cells and showed efficient reactivity against various tumor types. Seven MAGE-specific TCRs were identified, expanding the pool of cancer patients eligible for TCR gene therapy.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Chemistry, Analytical
Bart Claushuis, Robert A. Cordfunke, Arnoud H. de Ru, Annemarie Otte, Hans C. van Leeuwen, Oleg I. Klychnikov, Peter A. van Veelen, Jeroen Corver, Jan W. Drijfhout, Paul J. Hensbergen
Summary: Proteases are enzymes that hydrolyze peptide bonds and play a crucial role in various biological processes. We developed a method to study the cleavage specificity of a group of bacterial metalloproteases and discovered new peptide substrates. Additionally, we characterized a new metalloprotease with a distinct cleavage specificity from the other two studied proteases.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Leoni Abendstein, Douwe J. Dijkstra, Rayman T. N. Tjokrodirijo, Peter A. van Veelen, Leendert A. Trouw, Paul J. Hensbergen, Thomas H. Sharp
Summary: The authors used cryoEM and MS techniques to investigate IgG3-mediated complement activation and provide the first structural insights into IgG3. IgG3 is distinct from other IgG subclasses due to its extended hinge, allotypic diversity, and enhanced effector functions. However, the lack of structural information has limited its use as an immunotherapeutic candidate.
NATURE COMMUNICATIONS
(2023)
Correction
Cell Biology
Birol Cabukusta, Ilana Berlin, Daphne M. van Elsland, Iris Forkink, Menno Spits, Anja W. M. de Jong, Jimmy J. L. L. Akkermans, Ruud H. M. Wijdeven, George M. C. Janssen, Peter A. van Veelen, Jacques Neefjes