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)
Review
Immunology
Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock
Summary: Loss of MHC I antigen presentation is common in many cancers, which may impair immune responses and affect the efficacy of immunotherapy. Studies have discussed underlying mechanisms through which some cancers evade immune killing by shutting down the MHC I pathway, and proposed potential strategies to overcome this limitation.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
Review
Biochemistry & Molecular Biology
M. L. M. Jongsma, J. Neefjes, R. M. Spaapen
Summary: MHC-I molecules present a blueprint of the intracellular proteome to T cells for immune response, but pathogens and tumor cells can downmodulate MHC-I mediated antigen presentation to evade immune surveillance. While the fundamental rules of antigen presentation are well understood, new modules of regulation in this system continue to be uncovered.
MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Lei Zhan, Junhui Zhang, Jing Zhang, Xiaojing Liu, Suding Zhu, Yuchuan Shi, Yu He, Wenyan Wang, Yijing Wei, Zhenhai Tang, Guo Chen, Bing Wei, Yunxia Cao
Summary: In this study, the researchers found that upregulated autophagy and decreased expression of MHC-I and NLRC5 were associated with endometrial cancer (EC). Inhibition of autophagy was found to suppress MHC-I gene expression. They also discovered that LC3 interacted with NLRC5 to inhibit the NLRC5-mediated MHC-I antigen presentation pathway. These findings suggest that inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy for EC management.
Review
Immunology
Freidrich M. Cruz, Amanda Chan, Kenneth L. Rock
Summary: Phagocytes, particularly dendritic cells, play a crucial role in reporting antigen information to CD8 T cells through a process called cross-presentation. This process allows CD8 T cells to detect and eliminate abnormal cells. Phagosomes are key hubs in the cross-presentation process, where antigens can be cross-presented through different pathways. Understanding the molecular components and mechanisms involved in these processes is still an ongoing research area.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Immunology
Francois-Xavier Mauvais, Peter van Endert
Summary: The critical role of conventional dendritic cells in the immune response to tumors and pathogens is well-established. However, various other cell types, including myeloid, lymphoid, endothelial, epithelial, and stromal cells, have been shown to also possess the ability to cross-present antigens. This review analyzes the literature on this topic, discussing the antigens and readouts used, mechanistic insights, and in vivo experimentation. While many studies rely on artificial systems, there is evidence to suggest that cross-presentation by non-dendritic cells may have significant implications in anti-tumor immunity and autoimmunity.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Oncology
Priyanka S. Rana, James J. Ignatz-Hoover, James J. Driscoll
Summary: Proteasomes are complex protein-degrading machines that regulate the elimination of intracellular proteins. Immunoproteasomes are a specialized variant that degrade proteins in cells exposed to oxidative stress and inflammation. They can be targeted for therapeutic purposes in the treatment of cancer and infectious diseases.
Article
Multidisciplinary Sciences
Lauren E. Stopfer, Nicholas J. Rettko, Owen Leddy, Joshua M. Mesfin, Eric Brown, Shannon Winski, Bryan Bryson, James A. Wells, Forest M. White
Summary: Combining multiple therapeutic strategies may improve survival benefits for NRAS/BRAF mutant melanoma patients. This study utilized immunopeptidomics to measure the impact of MEK inhibition on anti-tumor immunity and identified enhanced expression of specific tumor antigens following therapy. Targeting these upregulated tumor antigens can enhance cell killing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
David H. Margulies, Jiansheng Jiang, Javeed Ahmad, Lisa F. Boyd, Kannan Natarajan
Summary: Peptide loading of MHC-I molecules plays a critical role in the response of T cells to infections and tumors. Recent advances in structural methods have improved our understanding of the biophysical parameters that govern peptide selection, binding, and surface display. The current understanding of this cellular process is based on various approaches, and further studies are needed to explore its details and potential applications in immunization and therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jeff D. Colbert, Freidrich M. Cruz, Christina E. Baer, Kenneth L. Rock
Summary: This study reveals a molecular association between Tspan5 and MHC I molecules that is critical for the formation of MHC I nanoclusters and optimal T cell responses to antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Maria C. Tovar Fernandez, Ewa M. Sroka, Mathilde Lavigne, Aikaterini Thermou, Chrysoula Daskalogianni, Benedicte Manoury, Rodrigo Prado Martins, Robin Fahraeus
Summary: The accumulation of protein aggregates is toxic and its relation to diseases is still unclear. This study reveals that certain antigenic peptides can be presented to the MHC class I pathway via autophagy. The presentation of peptides derived from the viral EBNA1 protein was not affected by autophagy suppression, while the presentation of ovalbumin was suppressed. The study also suggests that the relative levels of protein expression do not affect autophagy-mediated antigen presentation.
CELLULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuki Uchihara, Tiara Bunga Mayang Permata, Hiro Sato, Reika Kawabata-Iwakawa, Sayako Katada, Wenchao Gu, Sangeeta Kakoti, Motohiro Yamauchi, Reona Kato, Soehartati Gondhowiardjo, Naoki Hosen, Takaaki Yasuhara, Atsushi Shibata
Summary: This study reveals that DNA damage signaling can produce immunogenic antigens by utilizing the machinery of PRT/NMD. DNA damage upregulates HLA class I antigen presentation, and antigen production is essential. Additionally, the pioneer translation factor CBP20, which initiates nonsense-mediated mRNA decay, plays a critical role in antigen production.
Article
Clinical Neurology
Z. Fei, B. Pan, R. Pei, S. Ye, Z. Wang, L. Ma, R. Zhang, C. Li, Xi Du, Haijun Cao
Summary: This study investigated the neuroprotective effects and potential mechanisms of different IVIG in 3xTg-AD mice. The results showed that only IVIG-C had significant neuroprotective effects, which were associated with the inhibition of APP-MHC-I. IVIG may be a potential therapeutic for AD, but further research is needed to evaluate its functionality.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Engineering, Biomedical
Xiaodi Li, Pengfei Yuan, Haiyuan Yang, Xiaoqing Zong, Caiqi Yang, Xinjie Chen, Yuchao Li, Xiaodie Yan, Yaoqi Wen, Tianci Zhu, Qian Zhang, Wei Xue, Jian Dai
Summary: A novel virus-like nanotherapeutic (siRNA@HCM) is developed to enhance the antitumor immune response. It achieves this by improving tumor intrinsic MHC-I antigen presentation and promoting dendritic cell maturation. The use of siRNA@HCM also turns cold tumors into hot tumors and enhances the therapeutic effect of programmed death-1 inhibitor.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Multidisciplinary Sciences
Irini Evnouchidou, Pascal Chappert, Samira Benadda, Andres Zucchetti, Mirjana Weimershaus, Marcelle Bens, Vivien Caillens, Despoina Koumantou, Sophie Lotersztajn, Peter van Endert, Jean Davoust, Pierre Guermonprez, Claire Hivroz, David A. Gross, Loredana Saveanu
NATURE COMMUNICATIONS
(2020)
Article
Endocrinology & Metabolism
Claire-Marine Berat, Sebastian Montealegre, Arnaud Wiedemann, Malou Le Corronc Nuzum, Amelie Blondel, Hugo Debruge, Aline Cano, Brigitte Chabrol, Celia Hoebeke, Michel Polak, Athanasia Stoupa, Francois Feillet, Stephanie Torre, Nathalie Boddaert, Henri Bruel, Magalie Barth, Lena Damaj, Marie-Therese Abi-Warde, Alexandra Afenjar, Jean-Francois Benoist, Marine Madrange, Laure Caccavelli, Perrine Renard, Arnaud Hubas, Patrick Nusbaum, Clement Pontoizeau, Stephanie Gobin, Peter van Endert, Chris Ottolenghi, Alice Maltret, Pascale de Lonlay
Summary: TANGO2 disease is a severe inherited disorder characterized by neurodevelopmental delay, acute metabolic crises, and hypothyroidism, with significant intrafamilial clinical variability. Triggers of metabolic crises in TANGO2 patients were identified, while primary mitochondrial defects are unlikely to be the cause of the disease.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Immunology
Carole Drajac, Daphne Laubreton, Quentin Marquant, Claire Chottin, Cecile Ferret, Edwige Bouguyon, Isabelle Schwartz-Cornil, Loredana Saveanu, Sabine Riffault, Delphyne Descamps
Summary: Research has shown that neonatal AMs have a relatively weak ability to produce IFN-I upon RSV infection, leading to ineffective virus replication control; however, the deletion of IRAP protein can significantly increase IFN-I production in neonatal AMs. Furthermore, experiments have demonstrated that newborn IRAP(KO) mice infected with RSV have higher levels of IFN-I in their lungs and eliminate the virus more efficiently.
MUCOSAL IMMUNOLOGY
(2021)
Editorial Material
Biology
Peter van Endert
Summary: Spliced peptides on tumor cells can stimulate an immune response, but algorithms are not very effective in predicting which ones are actually present and functioning in vivo.
Article
Genetics & Heredity
Sebastian Montealegre, Elise Lebigot, Hugo Debruge, Norma Romero, Benedicte Heron, Pauline Gaignard, Antoine Legendre, Apolline Imbard, Stephanie Gobin, Emmanuelle Lacene, Patrick Nusbaum, Arnaud Hubas, Isabelle Desguerre, Aude Servais, Pascal Laforet, Peter van Endert, Francois Jerome Authier, Cyril Gitiaux, Pascale de Lonlay
Summary: This study characterizes the clinical and biological traits of two individuals with variants in ISCU and FDX2, finding that the individual with FDX2 variants is more severely affected.
NEUROLOGY-GENETICS
(2022)
Article
Cell Biology
Phillip Pymm, Stefan Tenzer, Edmund Wee, Mirjana Weimershaus, Anne Burgevin, Simon Kollnberger, Jan Gerstoft, Tracy M. Josephs, Kristin Ladell, James E. McLaren, Victor Appay, David A. Price, Lars Fugger, John I. Bell, Hansjoerg Schild, Peter van Endert, Maria Harkiolaki, Astrid K. N. Iversen
Summary: This study discovers that the cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a specific epitope in the human immunodeficiency virus are associated with enhanced immune control. The length and mutations of the epitope influence the CTL and NK cell responses, leading to viral escape.
Article
Oncology
Lucillia Bezu, Alejandra Wu Chuang, Allan Sauvat, Juliette Humeau, Wei Xie, Giulia Cerrato, Peng Liu, Liwei Zhao, Shuai Zhang, Julie Le Naour, Jonathan Pol, Peter van Endert, Oliver Kepp, Fabrice Barlesi, Guido Kroemer
Summary: This study investigates the anticancer effects of six local anesthetics used in clinical practice. The results suggest that local anesthetics induce immunogenic stress responses in cancer cells, leading to antitumor effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biophysics
Ambroise Marcais, Nizar Mahlaoui, Benedicte Neven, Fanny Lanternier, Emilie Catherinot, Helene Salvator, Morgane Cheminant, Maxime Jeljeli, Vahid Asnafi, Peter van Endert, Louis-Jean Couderc, Olivier Lortholary, Capucine Picard, Despina Moshous, Olivier Hermine, Alain Fischer, Felipe Suarez
Summary: Allo-HSCT is an effective and safe treatment for young adults with primary immunodeficiency disease (PID), with acceptable toxicity and clinical improvement.
BONE MARROW TRANSPLANTATION
(2022)
Article
Chemistry, Medicinal
Dionisios Vourloumis, Ioannis Mavridis, Alexandros Athanasoulis, Ioannis Temponeras, Despoina Koumantou, Petros Giastas, Anastasia Mpakali, Victoria Magrioti, Jacqueline Leib, Peter van Endert, Efstratios Stratikos, Athanasios Papakyriakou
Summary: A highly selective synthetic method for functionalization of the alpha-hydroxy-beta-amino acid scaffold of an aminopeptidase inhibitor has been discovered. Structural studies revealed that interactions with the GAMEN loop play a key role in the potency and selectivity of the inhibitor. This study suggests that alpha-hydroxy-beta-amino acid derivatives could serve as useful drug leads for aminopeptidases.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Immunology
Jonas Kuiper, Peter van Endert
Summary: The Black Death, caused by Yersinia pestis infection, was a devastating pandemic in the 14th century that posed a significant challenge to human immune defenses. A recent study suggests that a genetic variant in an antigen-processing gene may have provided survival advantage during the plague and underwent rapid genomic selection in Europeans.
TRENDS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ayse Yilmaz, Chiara Guerrera, Emmanuelle Waeckel-Enee, Joanna Lipecka, Barbara Bertocci, Peter van Endert
Summary: Insulin-degrading enzyme (IDE) is mainly localized in the cytosol and has additional functions beyond insulin degradation. It interacts with multiple mitochondrial ribosomal proteins and proteins involved in mitochondrial complex synthesis and assembly. The mitochondrial interactomes of wild type and mutant IDE are similar and do not reveal proteolytic IDE substrates. IDE may have non-proteolytic functions in mitochondria, acting as a chaperone and contributing to protein homeostasis and stress responses.
Review
Immunology
Irini Evnouchidou, Despoina Koumantou, Mathilde Nugue, Loredana Saveanu
Summary: Antigen-trimming aminopeptidases, belonging to the oxytocinase subfamily of M1 metallopeptidases, have been extensively studied for their ability to modify antigenic precursors and generate major histocompatibility class-I ligands. These enzymes have been associated with autoimmune diseases, cancers, and infections, and recent research has raised new questions about their functions.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Samira Benadda, Mathilde Nugue, Despoina Koumantou, Marcelle Bens, Mariacristina De Luca, Olivier Pelle, Renato C. Monteiro, Irini Evnouchidou, Loredana Saveanu
Summary: This study investigated the involvement of endosomal signaling in the function of human receptors for Fc immunoglobulin fragments (FcRs). The results showed that Fc alpha RI was targeted directly to lysosomes, while Fc gamma RIIA and Fc gamma RI were internalized in specific endosomal compartments described by IRAP. The destabilization of Fc gamma R endosomal signaling compromised cytokine secretion and macrophage ability to kill tumor cells by ADCC.
Review
Biochemistry & Molecular Biology
Irini Evnouchidou, Vivien Caillens, Despoina Koumantou, Loredana Saveanu
Summary: This study reviews the molecular mechanisms of TCR endocytosis and recycling and discusses the impact of endosomal TCR signaling on T cell activation.
BIOMEDICAL JOURNAL
(2022)
Article
Cell Biology
Yamina Hamel, Francois-Xavier Mauvais, Marine Madrange, Perrine Renard, Corinne Lebreton, Ivan Nemazanyy, Olivier Pelle, Nicolas Goudin, Xiaoyun Tang, Mathieu P. Rodero, Caroline Tuchmann-Durand, Patrick Nusbaum, David N. Brindley, Peter van Endert, Pascale de Lonlay
Summary: Mutations in LPIN1 gene lead to lipin1 deficiency, causing recurrent rhabdomyolysis. Intervention with hydroxychloroquine may improve symptoms in patients by blocking TLR9 activation.
CELL REPORTS MEDICINE
(2021)
