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.
Article
Multidisciplinary Sciences
Sagar Gupta, Santrupti Nerli, Sreeja Kutti Kandy, Glenn L. Mersky, Nikolaos G. Sgourakis
Summary: The study identified discrete peptide backbone conformations in pHLA complexes through analysis of crystal structures in the HLA3DB database. Leveraging these conformations, the authors developed a comparative modeling method named RepPred, which outperforms existing approaches in accurately predicting nonamer pHLA structures.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dannielle Wellington, Zixi Yin, Zhanru Yu, Raphael Heilig, Simon Davis, Roman Fischer, Suet Ling Felce, Elie Antoun, Philip Hublitz, Ryan Beveridge, Danning Dong, Guihai Liu, Xuan Yao, Yanchun Peng, Benedikt M. Kessler, Tao Dong
Summary: This study reveals that mutations in flanking regions of SARS-CoV-2 epitopes can affect proteasomal processing and T cell activation, leading to immune escape or enhancement. These findings have important implications for the design of COVID-19 vaccines.
Article
Biochemistry & Molecular Biology
Marta Gomez-Perosanz, Jose L. Sanchez-Trincado, Miguel Fernandez-Arquero, John Sidney, Alessandro Sette, Esther M. Lafuente, Pedro A. Reche
Summary: This study identified and characterized 23 conserved HRV-specific CD8 T cell epitopes on PBMCs from 14 HLA I typed subjects, confirming peptide-specific IFN gamma production and binding to the relevant HLA I for nine of these epitopes. The study also validated cytotoxicity mediated by A*02:01-restricted epitopes and discovered an unusually long 16-mer epitope peptide restricted by A*02:01. These HRV-specific CD8 T cell epitopes are expected to elicit CD8 T cell responses in up to 87% of the population and could be crucial for developing an HRV vaccine.
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)
Review
Immunology
Joerg Christoph Prinz
Summary: HLA-associated autoimmune diseases are likely caused by T-cell-mediated autoimmune responses against self-peptides presented by HLA molecules. Limited knowledge of autoantigens hinders the understanding of autoimmune pathogenesis due to antigen processing complexity and T-cell receptor polyspecificity. In HLA-class I-associated diseases, autoimmune responses target cells expressing parental proteins, while in HLA-class II-associated diseases, immunogenic peptides can originate from both extracellular and cellular self-proteins.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shira Weingarten-Gabbay, Susan Klaeger, Siranush Sarkizova, Leah R. Pearlman, Da-Yuan Chen, Kathleen M. E. Gallagher, Matthew R. Bauer, Hannah B. Taylor, W. Augustine Dunn, Christina Tarr, John Sidney, Suzanna Rachimi, Hasahn L. Conway, Katelin Katsis, Yuntong Wang, Del Leistritz-Edwards, Melissa R. Durkin, Christopher H. Tomkins-Tinch, Yaara Finkel, Aharon Nachshon, Matteo Gentili, Keith D. Rivera, Isabel P. Carulli, Vipheaviny A. Chea, Abishek Chandrashekar, Cansu Cimen Bozkus, Mary Carrington, Nina Bhardwaj, Dan H. Barouch, Alessandro Sette, Marcela Maus, Charles M. Rice, Karl R. Clauser, Derin B. Keskin, Daniel C. Pregibon, Nir Hacohen, Steven A. Carr, Jennifer G. Abelin, Mohsan Saeed, Pardis C. Sabeti
Summary: T cell-mediated immunity plays a crucial role in controlling SARS-CoV-2 infection, with some peptides derived from internal out-of-frame ORFs in spike and nucleocapsid eliciting stronger T cell responses than canonical peptides. Early expressed viral proteins contribute more to HLA-I presentation and immunogenicity, providing insights for vaccine development and immune monitoring.
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
Medicine, Research & Experimental
Concetta Ragone, Carmen Manolio, Angela Mauriello, Beatrice Cavalluzzo, Franco M. Buonaguro, Maria Lina Tornesello, Maria Tagliamonte, Luigi Buonaguro
Summary: This study demonstrates for the first time a high degree of homology in linear sequence, structure, and conformation between microbiota and tumor-associated antigens, suggesting that the anti-microbiota T cell memory in cancer patients may play a role in controlling cancer growth. This finding may have implications for the development of a novel preventive anti-cancer vaccine strategy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Emma T. M. Peereboom, Benedict M. Matern, Toshihide Tomosugi, Matthias Niemann, Julia Drylewicz, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Franka E. van Reekum, Marianne C. Verhaar, Elena G. Kamburova, Marc A. J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G. J. Tilanus, Christien E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Marielle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Azam Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Frederike J. Bemelman, Aiko P. J. de Vries, Johan W. de Fijter, Michiel G. H. Betjes, Dave L. Roelen, Frans H. Claas, Henny G. Otten, Sebastiaan Heidt, Arjan D. van Zuilen, Takaaki Kobayashi, Kirsten Geneugelijk, Eric Spierings
Summary: The presence of pre-transplant donor-reactive CD4(+) memory T-helper cells may increase the risk of graft failure following kidney transplantation, as shown by the significant association between Shared T-cell EPitopes (STEP) score and the 10-year risk of death-censored kidney graft failure.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Martin G. Klatt, Tao Dao, Zhiyuan Yang, Jianying Liu, Sung Soo Mun, Megan M. Dacek, Hanzhi Luo, Thomas J. Gardner, Christopher Bourne, Leila Peraro, Zita E. H. Aretz, Tanya Korontsvit, Michael Lau, Michael G. Kharas, Cheng Liu, David A. Scheinberg
Summary: Mass spectrometry identified a non-immunogenic HLA ligand as a target for CAR T-cell therapy, which showed broad effectiveness against multiple cancer types, particularly hematologic cancers, and had no toxic effects on healthy cells.
Article
Biochemical Research Methods
Iliana Papadopoulou, An-Phi Nguyen, Anna Weber, Maria Rodriguez Martinez
Summary: This study presents a computational pipeline called DECODE that can extract binding rules from black-box models designed to predict TCR-epitope binding. The pipeline can help improve understanding of sequence motifs underlying TCR binding and facilitate research into current immunotherapeutic challenges.
Article
Multidisciplinary Sciences
Angela R. Smith, Jesus A. Alonso, Cory M. Ayres, Nishant K. Singh, Lance M. Hellman, Brian M. Baker
Summary: This study shows that modifications at primary anchors, even without structural impact, can significantly affect T cell recognition depending on the TCR. The impact of peptide anchor modification can be sensed by a TCR at regions distant from the modification site, indicating a through-protein mechanism. These findings have implications for the use of anchor-modified peptides and predicting the immunogenicity of tumor neoantigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
E. Moreno-Cortes, J. V. Forero-Forero, P. A. Lengerke-Diaz, J. E. Castro
Summary: The rapid growth of CAR T-cell therapy in clinical trials, particularly in the field of hematologic malignancies, is evident. Apart from China and the USA, other countries are also starting to participate in research in this area, with the expectation of more CAR T-cell therapy clinical trials in the future.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Immunology
Johnathan Canton, Hanna Blees, Conor M. Henry, Michael D. Buck, Oliver Schulz, Neil C. Rogers, Eleanor Childs, Santiago Zelenay, Hefin Rhys, Marie-Charlotte Domart, Lucy Collinson, Andres Alloatti, Cara J. Ellison, Sebastian Amigorena, Venizelos Papayannopoulos, David C. Thomas, Felix Randow, Caetano Reis e Sousa
Summary: DNGR-1 is a dedicated cross-presentation receptor that promotes phagosomal rupture, allowing corpse-associated antigens to access the major histocompatibility complex class I antigen processing pathway. This mechanism reveals the existence of innate immune receptors that couple ligand binding and endocytic vesicle damage to regulate adaptive immunity.
Article
Immunology
Saghar Kaabinejadian, Carolina Barra, Bruno Alvarez, Hooman Yari, William H. Hildebrand, Morten Nielsen
Summary: Mass spectrometry-based immunopeptidomics is an important technique in biomedical applications, but the complexity of the data and the lack of appropriate tools have hindered its large-scale application. In this study, a new tool called MHCMotifDecon is presented, which accurately deconvolutes immunopeptidome datasets and helps identify and characterize HLA binding motifs, thus facilitating the discovery of new T cell targets.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Martina Gilodi, Simonetta Lisi, Erika F. Dudas, Marco Fantini, Rita Puglisi, Alexandra Louka, Paolo Marcatili, Antonino Cattaneo, Annalisa Pastore
Summary: This study describes the selection and characterization of a new intracellular antibody against TDP-43 from a llama nanobody library. The findings illustrate an effective therapeutic strategy for mitigating TDP-43 proteinopathy and provide a potential new tool for diagnostics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Julio Vacacela, Anna-Lisa Schaap-Johansen, Patricia Manikova, Paolo Marcatili, Marta Prado, Yi Sun, Jon Ashley
Summary: Inspired by molecularly imprinted polymers, this study demonstrates the protein-target mediated synthesis of enzyme-generated aptamers (EGAs) for the first time. Two mechanisms were identified for the formation of EGAs, including binding of random sequences to the target and dynamic competition between TdT enzyme and the target protein. This new approach increases the stringency of EGA-based screening and offers a rational design method for aptamer development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Magnus Haraldson Hoie, Erik Nicolas Kiehl, Bent Petersen, Morten Nielsen, Ole Winther, Henrik Nielsen, Jeppe Hallgren, Paolo Marcatili
Summary: Recent advances in machine learning and natural language processing have enabled accurate prediction of protein structures and functions, with NetSurfP-3.0 standing out as a tool with drastically improved runtime and reliable prediction performance.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Simon Gregersen, Margarita Pertseva, Paolo Marcatili, Susan Lovstad Holdt, Charlotte Jacobsen, Pedro J. Garcia-Moreno, Egon Bech Hansen, Michael Toft Overgaard
Summary: Seaweeds have been used as stabilizing agents in the food industry for a long time, and they also contain a significant amount of protein. This study combined transcriptomics, proteomics, and bioinformatics to analyze the protein composition in two pilot-scale extracts from Eucheuma denticilatum obtained via hot-water extraction. Despite the poor quality of the extracted protein, the analysis identified three previously uncharacterized proteins as the majority of quantified protein in the extracts (>75%). The study highlights the potential of quantitative proteomics for characterizing alternative protein sources in foods and evaluating the efficiency of protein extraction processes.
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
Zeynep Kosaloglu-Yalcin, Nina Blazeska, Randi Vita, Hannah Carter, Morten Nielsen, Stephen Schoenberger, Alessandro Sette, Bjoern Peters
Summary: CEDAR is a freely accessible database and analysis resource for cancer epitopes, which are molecular targets recognized by anti-cancer immune cells. Detailed knowledge of cancer epitopes is crucial for understanding and planning cancer prevention, treatment, and immune responses.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Alessandro Montemurro, Leon Eyrich Jessen, Morten Nielsen
Summary: T cell receptors (TCR) play a crucial role in the specificity of T cells, but predicting the interaction between TCR and MHC-peptide complexes remains challenging. This study proposes a framework and a machine learning model for predicting TCR specificity with high accuracy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Loulieta Nazerai, Shona Caroline Willis, Patricio Yankilevich, Luca Di Leo, Francesca Maria Bosisio, Alex Frias, Corine Bertolotto, Jacob Nersting, Maria Thastrup, Soren Buus, Allan Randrup Thomsen, Morten Nielsen, Kristoffer Staal Rohrberg, Kjeld Schmiegelow, Daniela De Zio
Summary: This study used the drug 6TG to induce mutations in tumor cells and increase the level of neoepitopes, enhancing the immune response. 6TG exposure increased tumor mutational burden and reshaped the tumor microenvironment, making the tumors more responsive to immune-checkpoint blockade.
Article
Immunology
Timothy Connelley, Annalisa Nicastri, Tara Sheldrake, Christina Vrettou, Andressa Fisch, Birkir Reynisson, Soren Buus, Adrian Hill, Ivan Morrison, Morten Nielsen, Nicola Ternette
Summary: This study used immunopeptidomics to study the repertoire of peptides presented by Theileria parva-infected cells. A comprehensive dataset of 74 BoLA-I and 15 BoLA-DR-presented peptides, based on different BoLA genotypes, was generated. The study demonstrated the utility of immunopeptidomics as a method to identify novel T-cell antigens for T. parva.
Article
Biology
Helle Rus Povlsen, Amalie Kai Bentzen, Mohammad Kadivar, Leon Eyrich Jessen, Sine Reker Hadrup, Morten Nielsen, K. Christopher Garcia
Summary: Novel single-cell-based technologies enable high-throughput matching of T cell receptor (TCR) sequences with their cognate peptide-MHC recognition motif. A data-driven method called ITRAP is proposed to filter out likely artifacts and generate large sets of TCR-pMHC sequence data with high specificity and sensitivity. This approach has been validated in virus-specific T cell responses across multiple healthy donors.
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
Sandra Eltschkner, Samantha Mellinger, Soren Buus, Morten Nielsen, Kajsa M. M. Paulsson, Karin Lindkvist-Petersson, Helena Westerdahl
Summary: Long-distance migratory animals such as birds and bats have evolved a unique adaptive immunity with highly duplicated Major Histocompatibility Complex (MHC) genes to withstand diverse pathogens. A study on the MHC class I protein, Acar3, from the great reed warbler reveals a peculiar peptide-binding mode that potentially facilitates interactions with innate immune receptors. The investigation highlights the importance of studying the immune system of wild animals to uncover unique immune mechanisms absent in humans and model organisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Mathematical & Computational Biology
Yuchen Li, Peter Wad Sackett, Morten Nielsen, Carolina Barra
Summary: This article introduces a new protein allergenicity prediction method, which introduces MHC presentation propensity as a novel feature to overcome the limitations of previous methods in accurately predicting allergenicity when similarity diminishes.
BIOINFORMATICS ADVANCES
(2023)
Meeting Abstract
Physiology
M. S. Khilji, P. Faridi, E. Pinheiro-Machado, C. Hoefner, T. Dahlby, R. Aranha, S. Buus, M. Nielsen, J. Klusek, T. Mandrup-Poulsen, K. Pandey, A. W. Purcell, M. T. Marzec
Article
Medicine, Research & Experimental
Nikolaj Pagh Kristensen, Christina Heeke, Siri A. Tvingsholm, Annie Borch, Arianna Draghi, Michael D. Crowther, Ibel Carri, Kamilla K. Munk, Jeppe Sejero Holm, Anne-Mette Bjerregaard, Amalie Kai Bentzen, Andrea M. Marquard, Zoltan Szallasi, Nicholas McGranahan, Rikke Andersen, Morten Nielsen, Goran B. Jonsson, Marco Donia, Inge Marie Svane, Sine Reker Hadrup
Summary: This study examined the frequency of neoepitope-specific CD8(+) T cells in tumor-infiltrating lymphocyte (TIL) infusion products and blood samples from melanoma patients who received adoptive cell therapy (ACT). The results showed that the frequency of neoepitope-specific CD8(+) T cells correlated with patient survival, and these cells were unique to responders of TIL-ACT. Additionally, a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8(+) T cells in the infusion product.
JOURNAL OF CLINICAL INVESTIGATION
(2022)