Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Saskia V. Vijver, Sarah Danklmaier, Lisa Pipperger, Raphael Gronauer, Gabriel Floriani, Hubert Hackl, Krishna Das, Guido Wollmann
Summary: This study aimed to identify the anti-viral T cells raised by VSV-GP virotherapy in C57BL/6J mice using a multi-level adapted bioinformatics approach. The top-ranked viral epitopes triggering IFN-gamma secretion due to T cell activation were identified and validated. Overall, this identification of VSV-GP T cell epitopes enables comprehensive monitoring of anti-viral T cell responses and supports the development of novel VSV-GP variants.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Fisheries
C. Kossack, N. Fuentes, K. Maisey
Summary: This study provides a prediction of B-cell and T-cell antigenic epitopes for ISAV proteins in farmed Atlantic salmon. The predicted epitopes have the potential to elicit an immune response in salmon and serve as peptides for future vaccine development against ISAV. The ability to model and predict these interactions is crucial for understanding unknown epitope specificity and MHC binding.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Edlainne Pinheiro Ferreira-Sena, Daiana de Jesus Hardoim, Flavia de Oliveira Cardoso, Luiz Ney d'Escoffier, Isabela Ferreira Soares, Joao Pedro Rangel da Silva Carvalho, Ricardo Almir Angnes, Stenio Perdigao Fragoso, Carlos Roberto Alves, Salvatore Giovanni De-Simone, Josue da Costa Lima-Junior, Alvaro Luiz Bertho, Tania Zaverucha-do-Valle, Franklin Souza da Silva, Katia da Silva Calabrese
Summary: Leishmaniasis is a complex and diverse disease that is considered a major public health problem. Despite the availability of treatment options, there are currently no vaccines for cutaneous leishmaniasis. This study focused on the prediction and characterization of antigenic epitopes that could interact with major histocompatibility complex class I in mice or humans. Through a combination of immunogenicity prediction and interaction assays, nine antigenic peptides were identified as strong candidates for the development of a peptide vaccine against leishmaniasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Laura F. Fielden, Jakob D. Busch, Sandra G. Merkt, Iniyan Ganesan, Conny Steiert, Hanna B. Hasselblatt, Jon V. Busto, Christophe Wirth, Nicole Zufall, Sibylle Jungbluth, Katja Noll, Julia M. Dung, Ludmila Butenko, Karina von der Malsburg, Hans-Georg Koch, Carola Hunte, Martin van der Laan, Nils Wiedemann
Summary: The presequence translocase of the mitochondrial inner membrane (TIM23) is the major route for importing nuclear-encoded proteins into mitochondria. Tim17, a subunit of TIM23, interacts with preproteins in the matrix or inner membrane for protein translocation. The negative charges in Tim17 initiate the translocation mechanism and release the preproteins into the inner membrane.
Article
Immunology
Paula Ruibal, Ian Derksen, Marjolein van Wolfswinkel, Linda Voogd, Kees L. M. C. Franken, Angela F. El Hebieshy, Thorbald van Hall, Tom A. W. Schoufour, Ruud H. Wijdeven, Tom H. M. Ottenhoff, Ferenc A. Scheeren, Simone A. Joosten
Summary: There is growing interest in HLA-E-restricted T-cell responses as a potential vaccination target. This study developed a method for efficient peptide thermal exchange on HLA-E monomers and multimers, allowing high-throughput production. The optimized conditions for detection and analysis of peptide-specific T cells revealed new insights into the interaction between HLA-E and NKG2A/CD94 receptors.
Review
Immunology
Laura Santambrogio
Summary: Advances in the analysis of the MHC class II ligandome have increased our understanding of the factors that regulate the range and selection of presented peptides, and the landscape is highly sensitive to changes in protein composition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Karin Schmidt, Matthias Leisegang, Peter-Michael Kloetzel
Summary: The therapy of cancer by adoptive T cell transfer (ACT) requires T cell receptors (TCRs) with optimal affinity for HLA class I-bound peptides (pHLA-I). But not every patient responds to ACT. This study investigated the contribution of ERAP1 and ERAP2 to TCR recognition of cancer cells and found that ERAP2 plays a significant role in tumor epitope presentation and TCR recognition. These findings may have implications for future ACT design.
MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Yue Shen, Jerry M. Parks, Jeremy C. Smith
Summary: This study presents a method for classifying HLA class I molecules using three-dimensional structures, which improves the breadth, accuracy, stability, and flexibility of classification. The findings show that structural similarity is highly correlated with peptide binding specificity. This new classification is useful in peptide-based vaccine development and HLA-disease association studies.
JOURNAL OF IMMUNOLOGY
(2023)
Review
Immunology
Karolina D. Witt
Summary: MHC class I antigen processing is a less recognized area in nonviral host-pathogen interactions, involving immunology and cell biology. This review focuses on the MHC-I antigen processing pathway and alternative sources of antigens, particularly in the context of Mycobacterium tuberculosis (Mtb) as an intracellular pathogen. It explores how Mtb manipulates host immunity for survival and proposes directions for MHC-I-focused approaches in developing vaccines against tuberculosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
Article
Immunology
Tobias Held, Michael Basler, Klaus-Peter Knobeloch, Marcus Groettrup
Summary: ISG15, induced by type I IFNs, may enhance MHC-I restricted antigen presentation by promoting co-translational antigen processing, without directly inducing proteasomal degradation of ISG15 target proteins.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Fuxu Wang, Haoyan Wang, Lizhuang Wang, Haoyu Lu, Shizheng Qiu, Tianyi Zang, Xinjun Zhang, Yang Hu
Summary: This study introduces the MHCRoBERTa method, which uses RoBERTa pre-training approach to predict the binding affinity between type I MHC and peptides. Experimental results show that MHCRoBERTa outperforms other prediction methods, with a significant improvement on IC50 value, demonstrating its potential in cancer immunotherapy.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Evolutionary Biology
Gemma Palomar, Katarzyna Dudek, Ben Wielstra, Elizabeth L. Jockusch, Michal Vinkler, Jan W. Arntzen, Gentile F. Ficetola, Masatoshi Matsunami, Bruce Waldman, Martin Tesicky, Piotr Zielinski, Wieslaw Babik
Summary: The study found that in urodele amphibians, some APGs are closely linked to MHC I genes, and all APGs show signs of episodic positive selection. However, the detected gene duplications, putative gene losses, and divergent allelic lineages suggest that if there is coevolution between APGs and MHC I, it may be more complex than originally hypothesized.
GENOME BIOLOGY AND EVOLUTION
(2021)
Article
Cell Biology
Wisath Sae-Lee, Caitlyn L. McCafferty, Eric J. Verbeke, Pierre C. Havugimana, Ophelia Papoulas, Claire D. McWhite, John R. Houser, Kim Vanuytsel, George J. Murphy, Kevin Drew, Andrew Emili, David W. Taylor, Edward M. Marcotte
Summary: This study reveals the proteome and interactome of red blood cells using quantitative mass spectrometry and machine learning, and builds structural models of protein complexes. It provides a comprehensive resource for future research.
Article
Biochemical Research Methods
Malte Sielaff, Valentina Curella, Manjusha Neerukonda, Muhammad Afzal, Khaoula El Hassouni, Ute Distler, Detlef Schuppan, C. Friedrich H. Longin, Stefan Tenzer
Summary: A novel hybrid LC-MS approach was introduced for the quantitative proteome analysis of ATI extracts, showing high reproducibility and precision. The method was validated for different wheat species and environmental effects on ATI expression, demonstrating its potential for generating new hypotheses or assay development.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Irina Alberg, Stefan Kramer, Christian Leps, Stefan Tenzer, Rudolf Zentel
Summary: The study demonstrates that preventing the reorganization of micelles by core-crosslinking is crucial in reducing the interaction with plasma proteins.
MACROMOLECULAR BIOSCIENCE
(2021)
Article
Cell Biology
Madeleine Eichler, Ute Distler, Usman Nasrullah, Aswini Krishnan, Manuel Kaulich, Koraljka Husnjak, Wolfgang Eberhardt, Krishnaraj Rajalingam, Stefan Tenzer, Josef Pfeilschifter, Gergely Imre
Summary: This study uncovers a previously unknown mechanism of caspase-2 tumor suppressor function in human tumor cells, in which selective cleavage of p54nrb disrupts its role in RNA editing, transport, and transcriptional regulation, leading to reduced tumorigenic potential.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Nicola Hoppmann, Nora Heinig, Ute Distler, Ella Kim, Volker Lennerz, Yvonne Krauss, Ulrike Schumann, Alf Giese, Stefan Tenzer, Lynn Bitar, Mirko H. H. Schmidt
Summary: This study focuses on the role of stem cell-like glioma-propagating cells (GPCs) in the development and treatment resistance of glioblastoma multiforme. GPCs exhibit strong immunosuppressive activities, which limit the effectiveness of immunotherapies. The study shows that radio-selected GPCs with increased radio-resistance exhibit reduced immunogenic potential due to downregulation of antigen processing machinery, resulting in decreased MHC surface expression and weaker cytotoxic T lymphocyte recognition.
Article
Biology
Christina Wolf, Alireza Pouya, Sara Bitar, Annika Pfeiffer, Diones Bueno, Sabine Arndt, Stefan Tenzer, Federica Dal Bello, Caterina Vianello, Sandra Ritz, Jonas Schwirz, Kristina Dobrindt, Michael Peitz, Eva-Maria Hanschmann, Ibrahim Boussaad, Oliver Brustle, Marta Giacomello, Rejko Kruger, Axel Methner, Liliana Rojas-Charry, David Gomez-Zepeda, Pauline Mencke, Marion Silies, Oliver Brustle
Summary: GDAP1 mutations in Charcot-Marie-Tooth disease 4A inhibit the pyruvate dehydrogenase complex and restrict the localization of dynamin-related protein 1 in mitochondria through alterations of actin signaling. This study provides insights into the underlying mechanism of GDAP1-associated phenotypes and highlights the role of disrupted actin signaling in CMT4A pathophysiology.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemical Research Methods
Konstantin Bob, David Teschner, Thomas Kemmer, David Gomez-Zepeda, Stefan Tenzer, Bertil Schmidt, Andreas Hildebrandt
Summary: This study demonstrates the effectiveness of locality-sensitive hashing in signal classification in mass spectrometry raw data, achieving superior performance by balancing false-positive and false-negative rates through appropriate algorithm parameters. This approach significantly reduces data size while preserving important information in processing large-scale mass spectrometry data.
BMC BIOINFORMATICS
(2022)
Article
Virology
Linda Schweiger, Laura A. Lelieveld-Fast, Snjezana Mikulicic, Johannes Strunk, Kirsten Freitag, Stefan Tenzer, Albrecht M. Clement, Luise Florin
Summary: Human papillomaviruses (HPVs) cause significant burden on human population, leading to various cancers. The autophagy adaptor p62 is identified as a novel proviral factor in HPV16 infection. p62 interacts with virus-filled endosomes, accompanies the virus to the sites of viral transcription and replication, and plays a crucial role in HPV16 infection. Depletion of p62 enhances the targeting of viral components to autophagic structures and degradation of viral capsid protein.
Article
Microbiology
Jean Pierre Musabyimana, Ute Distler, Juliane Sassmannshausen, Christina Berks, Janice Manti, Sandra Bennink, Lea Blaschke, Paul-Christian Burda, Ansgar Flammersfeld, Stefan Tenzer, Che Julius Ngwa, Gabriele Pradel
Summary: S-adenosylmethionine synthetase (SAMS) is a crucial enzyme involved in the synthesis of S-adenosyl methionine (SAM), which plays important roles in cellular processes and may serve as a drug target in the malaria parasite.
Article
Biochemistry & Molecular Biology
Khaoula El Hassouni, Muhammad Afzal, Kim A. Steige, Malte Sielaff, Valentina Curella, Manjusha Neerukonda, Stefan Tenzer, Detlef Schuppan, Carl Friedrich Horst Longin, Patrick Thorwarth
Summary: Wheat proteins play an important role in nutrition, but can also cause adverse reactions. Through a genome wide association study, we identified quantitative trait loci that explain the genetic variation in wheat proteins. These loci can be used to select for low protein abundance in wheat cultivars for human health considerations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Katharina Bersching, Thomas Michna, Stefan Tenzer, Stefan Jacob
Summary: The dynamic interplay of signaling networks in cellular processes is characterized by reversible protein phosphorylation. Quantitative phospho-peptidomics has become a powerful platform for comprehensively analyzing the phosphorylation profile of living organisms. However, the presence of missing values in experimental procedures remains a major problem, reducing confidence in subsequent bioinformatic processing. By using data independent acquisition (DIA) in a filamentous fungus model organism, we were able to increase data completeness while maintaining data quality, providing a refined methodology for investigating signaling processes in filamentous fungi.
Article
Medicine, Research & Experimental
Christopher Nelke, Christina B. Schroeter, Frauke Stascheit, Niklas Huntemann, Marc Pawlitzki, Alice Willison, Saskia Raeuber, Nico Melzer, Ute Distler, Stefan Tenzer, Kai Stuehler, Andreas Roos, Andreas Meisel, Sven G. Meuth, Tobias Ruck
Summary: Therapeutic strategies targeting complement have revolutionized the treatment of myasthenia gravis. A combined proteomics and metabolomics approach was used to study a cohort of MG patients treated with eculizumab or azathioprine, as well as treatment-naive patients. Eculizumab was found to modulate the serum proteometabolome, affecting pathways related to oxidative stress, MAP kinase signaling, and lipid metabolism, particularly arachidonic acid signaling.
Article
Food Science & Technology
Muhammad Afzal, Malte Sielaff, Ute Distler, Detlef Schuppan, Stefan Tenzer, C. Friedrich H. Longin
Summary: Wheat processing quality is greatly influenced by proteins, but many people have inflammatory reactions to wheat proteins. The research applied proteomics to establish the flour reference proteome for five wheat species, finding significant differences in proteome profiles among species and many proteins related to quality, grain-starch synthesis, plant stress regulation, and allergic reactions. The expression of important wheat proteins is mainly determined by genetics, enabling the selection of improved cultivars, and einkorn wheat has lower quantities of potential allergens and immunogenic amylase trypsin inhibitors. Clinical studies are urgently needed, using the developed reference proteomes to design representative test diets.
NPJ SCIENCE OF FOOD
(2023)
Article
Biochemical Research Methods
David Gomez-Zepeda, Thomas Michna, Tanja Ziesmann, Ute Distler, Stefan Tenzer
Summary: This study introduces a workflow combining Skyline for MS1 feature extraction with HowDirty, an R-markdown-based tool, which automatically generates an interactive report on the molecular contaminant level in LC-MS data sets. The evaluation of ultrafiltration units from different providers using HowDirty allowed for the selection of filter units with the lowest contamination risk. HowDirty enables efficient evaluation of sample quality, minimizing the impact of common contaminants on LC-MS analyses.
Article
Biochemistry & Molecular Biology
Kai Chen, Xiyu Huang, Ute Distler, Stefan Tenzer, Ozlem Guenay-Esiyok, Nishith Gupta
Summary: This study reveals the working mechanism and importance of PtdSer flipping during the lytic cycle of Toxoplasma gondii. P4-ATPase1 and TgLem1 work together to translocate PtdSer across the plasma membrane, and their interaction is crucial for the reproduction, motility, egress, and invasion of tachyzoites. The P4-ATPase1-Lem1 heterocomplex could be a potential drug target in T. gondii.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Tabea Kuerten, Natascha Ihbe, Timo Ueberbach, Ute Distler, Malte Sielaff, Stefan Tenzer, Thomas Mittmann
Summary: Posttraumatic epilepsy (PTE) is a major public health concern and contributes significantly to global epilepsy cases. This study explores the role of the GABA(A)-stabilizing protein ubqln1 in mouse models of traumatic brain injury (TBI) and in vitro epilepsy. The findings suggest that ubqln1 and monoamine transmitter systems play a role in cortical network activity during posttraumatic epileptogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)