Article
Multidisciplinary Sciences
Alex M. Jaeger, Lauren E. Stopfer, Ryuhjin Ahn, Emma A. Sanders, Demi A. Sandel, William A. Freed-Pastor, William M. Rideout, Santiago Naranjo, Tim Fessenden, Kim B. Nguyen, Peter S. Winter, Ryan E. Kohn, Peter M. K. Westcott, Jason M. Schenkel, Sean-Luc Shanahan, Alex K. Shalek, Stefani Spranger, Forest M. White, Tyler Jacks
Summary: This study engineered an inducible affinity tag into the mouse MHC-I gene to precisely isolate MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma and lung adenocarcinoma in vivo. It revealed that peptide presentation in lung adenocarcinoma is not predictable by mRNA expression or translation efficiency and may be driven by post-translational mechanisms. Vaccination with peptides presented by lung adenocarcinoma induced CD8(+) T cell responses.
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)
Article
Biochemical Research Methods
Elena Lorente, Antonio J. Martin-Galiano, Dganit Melamed Kadosh, Alejandro Barriga, Juan Garcia-Arriaza, Carmen Mir, Mariano Esteban, Arie Admon, Daniel Lopez
Summary: This study utilized high-throughput mass spectrometry analysis to identify a large number of cell peptides bound to HLA-DR and -DP class II molecules, finding that these cell proteins were more acidic, abundant, and highly connected, but less hydrophilic compared to non-parental proteins.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Oncology
Georges Bedran, Hans-Christof Gasser, Kenneth Weke, Tongjie Wang, Dominika Bedran, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Catia Pesquita, Hakan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Palkowski, Maciej Pawlik, Maciej Parys, Robert O'Neill, Paul M. Brennan, Stefan N. Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fahraeus, Ted R. Hupp, Sachin Kote, Javier A. Alfaro
Summary: Using deep learning mass spectrometry, we developed a proteogenomic pipeline to discover noncanonical MHC class I-associated peptides (ncMAP) from noncoding regions. Analyzing data from 26 MHC class I immunopeptidomic studies across 11 different cancer types, we identified an atlas of 8,601 ncMAPs and suggested 17 cancer-selective ncMAPs as attractive therapeutic targets.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Immunology
Pankaj Kumar, Caitlin Boyne, Sydney Brown, Ayesha Qureshi, Peter Thorpe, Silvia A. Synowsky, Sally Shirran, Simon J. Powis
Summary: This study reveals the HLA-I ligandome in extracellular vesicles (EVs) from multiple cancer cell lines and identifies tumor-associated antigenic peptides. These findings contribute to a better understanding of tumor immune responses.
Article
Biochemical Research Methods
Arie Admon
Summary: This study suggests that there are likely no spliced peptides in the immunopeptidome, and if they exist at all, they are extremely rare. The claim is based on both biochemical and bioinformatics considerations, with evidence refuting the assignments of most of the immunopeptidome MS data to spliced peptides. Rigorous experimental methodology using heavy stable isotope peptides spiking into the immunoaffinity-purified mixtures of natural MHC peptides and analysis by highly reliable targeted MS is called for to confirm the presence of spliced MHC peptides.
MOLECULAR & CELLULAR PROTEOMICS
(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
Biochemical Research Methods
Kevin A. Kovalchik, Qing Ma, Laura Wessling, Frederic Saab, Jerome D. Duquette, Peter Kubiniok, David J. Hamelin, Pouya Faridi, Chen Li, Anthony W. Purcell, Anne Jang, Eustache Paramithiotis, Marco Tognetti, Lukas Reiter, Roland Bruderer, Joel Lanoix, Mathieu Courcelles, Pierre Thibault, Etienne Caron, Isabelle Sirois
Summary: Researchers have developed a semi-automated quality control software tool called MhcVizPipe (MVP) for rapid assessment of multiple MHC class I and II immunopeptidomic datasets generated by mass spectrometry. MVP provides a quick and comprehensive view of sample quality, composition, and MHC specificity to accelerate the decision-making process for data interpretation.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Immunology
Kathryn A. K. Finton, Mi-Youn Brusniak, Lisa A. Jones, Chenwei Lin, Andrew J. Fiore-Gartland, Chance Brock, Philip R. Gafken, Roland K. Strong
Summary: ARTEMIS is a novel platform for peptide discovery that addresses the limitations of traditional methods by providing a simple, robust, and flexible solution for discovering HLA-restricted peptides across a variety of laboratories. It combines new HLA-I discovery reagents, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon existing techniques. ARTEMIS is sensitive, adaptable, and cost-effective, making it widely applicable in general laboratories.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Catherine M. Ade, Matthew J. Sporn, Sudipto Das, Zhiya Yu, Ken-ichi Hanada, Yue A. Qi, Tapan Maity, Xu Zhang, Udayan Guha, Thorkell Andresson, James C. Yang
Summary: This article introduces a method of using mass spectrometry to identify common tumor-specific neoepitopes derived from mutated oncogenes, and develop TCRs based on these data. The results of the study show that this method successfully identified precise neoepitopes derived from KRAS, EGFR, BRAF, and PIK3CA presented by HLA-A*03:01 and/or HLA-A*11:01 across multiple biological replicates.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
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
Multidisciplinary Sciences
Gabriel K. Griffin, Jingyi Wu, Arvin Iracheta-Vellve, James C. Patti, Jeffrey Hsu, Thomas Davis, Deborah Dele-Oni, Peter P. Du, Aya G. Halawi, Jeffrey J. Ishizuka, Sarah Y. Kim, Susan Klaeger, Nelson H. Knudsen, Brian C. Miller, Tung H. Nguyen, Kira E. Olander, Malvina Papanastasiou, Suzanna Rachimi, Emily J. Robitschek, Emily M. Schneider, Mitchell D. Yeary, Margaret D. Zimmer, Jacob D. Jaffe, Steven A. Carr, John G. Doench, W. Nicholas Haining, Kathleen B. Yates, Robert T. Manguso, Bradley E. Bernstein
Summary: A CRISPR-Cas9 screen in mouse tumour models treated with immune checkpoint blockade identified SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity. Loss of SETDB1 leads to derepression of immune-stimulating genes and triggers TE-specific cytotoxic T cell responses, suggesting it as a potential target for immunotherapy in cancer treatment.
Article
Immunology
Gabriel Goncalves, Kerry A. Mullan, Divya Duscharla, Rochelle Ayala, Nathan P. Croft, Pouya Faridi, Anthony W. Purcell
Summary: Peptide vaccination is a promising strategy to induce T-cell mediated tumor killing. In this study, the effect of IFN gamma on TNBC cells was analyzed, revealing a significant remodeling of the immunopeptidome with increased diversity and abundance of peptides. The results suggest that cytokine stimulation can unveil a wider range of potential HLA-I and HLA-II vaccine targets, which has important implications for personalized cancer vaccination strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Katherine E. Scull, Kirti Pandey, Sri H. Ramarathinam, Anthony W. Purcell
Summary: Human leukocyte antigen (HLA) molecules present peptide antigens on cell surfaces, but unconventional peptide epitopes in the immunopeptidome require new methods for identification. A bioinformatics workflow incorporating standard transcriptomics software and novel computer programs successfully identified a large number of peptides and potential new epitopes.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Biochemical Research Methods
Lichao Zhang, Patrick L. McAlpine, Marlene L. Heberling, Joshua E. Elias
Summary: Recent advances in instrumentation have made mass spectrometry a powerful tool for discovering and quantifying naturally presented pMHC. A high-throughput and automated platform has been developed for sample preparation, significantly improving speed, sensitivity, and reproducibility. This platform can process up to 96 samples in 6 hours, yielding high-quality pMHC mixtures ready for mass spectrometry analysis.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Clinical Neurology
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yueng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanovic, Michael Weller, Guenter Eisele
ACTA NEUROPATHOLOGICA
(2018)
Article
Hematology
Tatjana Bilich, Annika Nelde, Leon Bichmann, Malte Roerden, Helmut R. Salih, Daniel J. Kowalewski, Heiko Schuster, Chih-Chiang Tsou, Ana Marcu, Marian C. Neidert, Maren Luebke, Jonas Rieth, Mirle Schemionek, Tim H. Bruemmendorf, Vladan Vucinic, Dietger Niederwieser, Jens Bauer, Melanie Maerklin, Janet K. Peper, Reinhild Klein, Oliver Kohlbacher, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanovic, Juliane S. Walz
Article
Biology
F. Tudor Ilca, Andreas Neerincx, Clemens Hermann, Ana Marcu, Stefan Stevanovic, Janet E. Deane, Louise H. Boyle
Article
Immunology
Maren Luebke, Stefanie Spalt, Daniel J. Kowalewski, Cosima Zimmermann, Liane Bauersfeld, Annika Nelde, Leon Bichmann, Ana Marcu, Janet Kerstin Peper, Oliver Kohlbacher, Juliane S. Walz, Vu Thuy Khanh Le-Trilling, Hartmut Hengel, Hans-Georg Rammensee, Stefan Stevanovic, Anne Halenius
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Oncology
Ana Marcu, Leon Bichmann, Leon Kuchenbecker, Daniel Johannes Kowalewski, Lena Katharina Freudenmann, Linus Backert, Lena Muehlenbruch, Andras Szolek, Maren Luebke, Philipp Wagner, Tobias Engler, Sabine Matovina, Jian Wang, Mathias Hauri-Hohl, Roland Martin, Konstantina Kapolou, Juliane Sarah Walz, Julia Velz, Holger Moch, Luca Regli, Manuela Silginer, Michael Weller, Markus W. Loffler, Florian Erhard, Andreas Schlosser, Oliver Kohlbacher, Stefan Stevanovic, Hans-Georg Rammensee, Marian Christoph Neidert
Summary: This study established the HLA Ligand Atlas, a comprehensive collection of immunopeptidomes from benign human tissue samples, enabling a balanced comparison between tumor and benign tissues. Results showed significant differences in immunopeptidomes between tissues and individuals, with the discovery of peptides from non-canonical genomic regions. This resource is a step towards defining safer tumor-associated targets for T-cell-based immunotherapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Peter Kubiniok, Ana Marcu, Leon Bichmann, Leon Kuchenbecker, Heiko Schuster, David J. Hamelin, Jerome D. Duquette, Kevin A. Kovalchik, Laura Wessling, Oliver Kohlbacher, Hans-Georg Rammensee, Marian C. Neidert, Isabelle Sirois, Etienne Caron
Summary: Understanding the composition of the MHCI immunopeptidome in different primary tissues is crucial for predicting T cell responses in different contexts. This study analyzed the MHCI immunopeptidome in various human and mouse tissues and found that different HLA allotypes have varying contributions to the overall composition. It also discovered that tissue specific and housekeeping MHCI peptides have distinct properties, and that evolutionarily hyperconserved proteins are the primary source of the immunopeptidome. The study also identified new components of the antigen processing and presentation network.
Article
Immunology
Fiamma Berner, David Bomze, Christa Lichtensteiger, Vincent Walter, Rebekka Niederer, Omar Hasan Ali, Nina Wyss, Jens Bauer, Lena Katharina Freudenmann, Ana Marcu, Eva-Maria Wolfschmitt, Sebastian Haen, Thorben Gross, Marie-Therese Abdou, Stefan Diem, Stella Knopefli, Tobias Sinnberg, Kathrin Hofmeister, Hung-Wei Cheng, Marieta Toma, Niklas Kluemper, Mette-Triin Purde, Oltin Tiberiu Pop, Ann-Kristin Jochum, Steve Pascolo, Markus Joerger, Martin Frueh, Wolfram Jochum, Hans-Georg Rammensee, Heinz Laeubli, Michael Hoelzel, Jacques Neefjes, Juliane Walz, Lukas Flatz
Summary: This study successfully identified self-antigens that likely mediate effective antitumor T cell responses in non-small cell lung cancer (NSCLC) using the DITAS method. Napsin A was identified as a self-antigen that elicited strong CD8(+) T cell responses. These findings may contribute to understanding the immune-related adverse events induced by immune checkpoint blockade therapy.
SCIENCE IMMUNOLOGY
(2022)