Article
Immunology
Patricia T. Illing, Andy van Hateren, Rachel Darley, Nathan P. Croft, Nicole A. Mifsud, Samuel King, Lyudmila Kostenko, Mandvi Bharadwaj, James McCluskey, Tim Elliott, Anthony W. Purcell
Summary: Abacavir hypersensitivity syndrome occurs in individuals with a specific gene expression, altering immune responses. Research shows that abacavir affects the assembly of HLA-B*57:01 complexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Physical
Honglin Xu, Kaiyuan Song, Lin-Tai Da
Summary: The study reveals the key intermediate states during the peptide loading process into TAPBPR-bound MHC-I and identifies the key structural factors responsible for the dynamics of peptide loading. The binding of TAPBPR at the MHC-I pocket-F reshapes the distant pocket-B through allosteric regulations, promoting the loading of the peptide. The partially loaded peptide weakens the stability of the TAPBPR-MHC interaction and affects the binding site through allosteric perturbations and direct contacts.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Review
Immunology
Esam Abualrous, Jana Sticht, Christian Freund
Summary: MHC loci are highly diverse in vertebrate genomes, with thousands of gene variants existing in the human population. Understanding the unique peptide binding profiles of MHC alleles and their interactions with regulators can lead to personalized immune modulation strategies for HLA-associated diseases.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ankur Saikia, Andries Hadeler, Pranathi Prasad, Martin Zacharias, Sebastian Springer
Summary: This study investigates the importance of peptide exchange in immunodominance and uncovers the mechanism of peptide exchange under low pH conditions. The results demonstrate that low pH triggers peptide exchange and provide insights into the individual steps of the exchange reaction.
Article
Pharmacology & Pharmacy
Natsumi Mizuno, Yoshiki Yanagawa
Summary: In this study, it was found that tofacitinib enhanced IFN-gamma-induced MHC II expression in macrophages by transcriptional regulation through induction of CIITA, while decreasing the expression of CD86.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Alexander Domnick, Christian Winter, Lukas Susac, Leon Hennecke, Mario Hensen, Nicole Zitzmann, Simon Trowitzsch, Christoph Thomas, Robert Tampe
Summary: In this study, the authors determine the structure of the editing module of the peptide loading complex (PLC) and reveal the communication between peptide-MHC I assembly and glycan processing. These findings are important for understanding the initiation of adaptive immune responses and the coordination of events in endoplasmic reticulum quality control.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Denise S. M. Boulanger, Leon R. Douglas, Patrick J. Duriez, Yoyel Kang, Neil Dalchau, Edd James, Tim Elliott
Summary: Tapasin, a component of MHC I peptide loading complex, plays a key role in shaping the hierarchy of CD8+ T-cell responses to tumors and pathogens by editing the repertoire of peptides presented at the cell surface. The level of tapasin expression affects peptide off-rate and abundance, and each peptide has a unique tapasin bonus fingerprint. Optimal tapasin expression level varies for each peptide in the immunopeptidome, depending on its off-rate and abundance. This finding is important in understanding immune responses and immune escape.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Ramesh Radhika, Milind S. Tullu, Sunil Karande, Umair Ahmed Bargir
Summary: Major Histocompatibility Complex (MHC) Class II deficiency is a rare autosomal recessive primary immunodeficiency caused by mutations in regulatory genes of MHC Class II proteins. This case report describes a 9-month-old girl presenting with repeated pneumonia, lymphocytopenia, and absence of HLA-DR expression on B cells, which led to the diagnosis of MHC Class II deficiency. Genetic analysis identified a homozygous mutation in the RFX-5 gene. Despite the patient's unfortunate outcome, the importance of prenatal diagnosis was emphasized to the parents.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Medicine, Research & Experimental
Shivai Gupta, Danmeng Li, David A. Ostrov, Cuong Q. Nguyen
Summary: This study proposes a novel therapeutic approach for SjS by blocking MHC class II I-Ag-7 antigen presentation in NOD mice. The results demonstrate that treating NOD mice with TATD or 8-Azaguanine can alleviate SjS symptoms and reduce the severity of the disease.
Article
Multidisciplinary Sciences
Ines Katharina Mueller, Christian Winter, Christoph Thomas, Robbert M. Spaapen, Simon Trowitzsch, Robert Tampe
Summary: This study reveals the molecular details of client recognition by the tapasin-ERp57 complex and emphasizes the importance of peptide proofreading. These findings contribute to understanding the selector function of tapasin and the mechanism by which multiple MHC I allomorphs are chaperoned during peptide loading and editing.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Dairy & Animal Science
Marion Rambault, Florence B. Gilbert, Philippe Roussel, Alexia Tessier, Pierre Germon, Nathalie Winter, Aude Remot
Summary: Bovine mastitis, caused by bacterial infection, not only leads to economic losses and health problems in animals, but also affects their welfare. Neutrophils play a crucial role in eliminating pathogens and are responsible for the increase in somatic cell count during mastitis. Recent research reveals that a subset of neutrophils expressing major histocompatibility complex class II have regulatory capacities in cattle, providing new insights into the immune response during mastitis.
JOURNAL OF DAIRY SCIENCE
(2023)
Review
Immunology
Jie Geng, Malini Raghavan
Summary: MHC-I molecules play a critical role in immune responses, and their conformational variations have profound implications for immunity.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Jerzy K. Kulski, Shingo Suzuki, Takashi Shiina
Summary: This study identifies and characterizes polymorphic human leukocyte antigen (HLA)-class II genes, MTCO3P1 pseudogene alleles, and indels of transposable elements linked to specific HLA-class II alleles. The research also reveals unique crossover sites between SNP-poor and SNP-rich genomic segments, with significant haplotype shuffling near putative recombination hotspots.
FRONTIERS IN GENETICS
(2021)
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
Biology
Orsolya Vincze, Claire Loiseau, Mathieu Giraudeau
Summary: High MHC class I diversity is associated with significantly lower richness of haemosporidian parasites in birds, indicating more efficient protection against intracellular pathogens. However, these associations were only detected when MHC diversity was assessed using cloning, suggesting the need for further clarification on the use of different genotyping methods for MHC loci quantification.
Article
Biochemistry & Molecular Biology
Florian A. Thesseling, Michael C. Hutter, Constanze Wiek, John P. Kowalski, Allan E. Rettie, Marco Girhard
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2020)
Article
Biochemistry & Molecular Biology
Luka de Vos, Ingela Gruenwald, Emma Grace Bawden, Joern Dietrich, Kathrin Scheckenbach, Constanze Wiek, Romina Zarbl, Friedrich Bootz, Jennifer Landsberg, Dimo Dietrich
Article
Chemistry, Medicinal
John P. Kowalski, Matthew G. McDonald, Robert D. Pelletier, Helmut Hanenberg, Constanze Wiek, Allan E. Rettie
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Matthew G. McDonald, Lindsay M. Henderson, Sutapa Ray, Catherine K. Yeung, Amanda L. Johnson, John P. Kowalski, Helmut Hanenberg, Constanze Wiek, Kenneth E. Thummel, Allan E. Rettie
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Article
Cell Biology
Laura Bergmann, Alexander Lang, Christoph Bross, Simone Altinoluk-Hambuechen, Iris Fey, Nina Overbeck, Anja Stefanski, Constanze Wiek, Andreas Kefalas, Patrick Verhuelsdonk, Christian Mielke, Dennis Sohn, Kai Stuehler, Helmut Hanenberg, Reiner U. Jaenicke, Juergen Scheller, Andreas S. Reichert, Mohammad Reza Ahmadian, Roland P. Piekorz
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.
Review
Gastroenterology & Hepatology
Roman Liebe, Irene Esposito, Hans H. Bock, Stephan vom Dahl, Jan Stindt, Ulrich Baumann, Tom Luedde, Verena Keitel
Summary: The term NAFLD was originally used to describe hepatic fat deposition in association with the metabolic syndrome. Secondary causes of fatty liver disease should be considered during diagnosis and treatment to halt disease progression, while genetic variants may play a role in the development and progression of liver diseases.
JOURNAL OF HEPATOLOGY
(2021)
Article
Immunology
Keven Hoerster, Markus Uhrberg, Constanze Wiek, Peter A. Horn, Helmut Hanenberg, Stefan Heinrichs
Summary: The study demonstrates the feasibility of genome editing in primary allogeneic NK cells to reduce their recognition and killing by mismatched T cells, making them potential off-the-shelf immune effectors for immunotherapy in cancer. Genetically engineered NK cells are functionally indistinguishable from unmodified cells with natural cytotoxicity towards AML cell lines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Einat Seidel, Liat Dassa, Shira Kahlon, Boaz Tirosh, Anne Halenius, Tal Seidel Malkinson, Ofer Mandelboim
Summary: The study reveals that the glycoprotein US9 of human cytomegalovirus downregulates the activating immune ligand MICA*008 by slow cleavage of its signal peptide, leading to retention and degradation in the endoplasmic reticulum (ER) via the ER quality control system.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Philipp Kolb, Katja Hoffmann, Annika Sievert, Henrike Reinhard, Eva Merce-Maldonado, Vu Thuy Khanh Le-Trilling, Anne Halenius, Dominique Guetle, Hartmut Hengel
Summary: HCMV uses multiple immune evasion strategies to counteract host immune control mechanisms, including the simultaneous expression of gp34 and gp68 to efficiently antagonize host FcγR activation through distinct but synergizing mechanisms. Gp34 enhances immune complex internalization, while gp68 inhibits host FcγR binding to immune complexes.
Article
Biochemistry & Molecular Biology
Sebastian Baasch, Piero Giansanti, Julia Kolter, Andre Riedl, Aaron James Forde, Solveig Runge, Simon Zenke, Roland Elling, Anne Halenius, Simone Brabletz, Hartmut Hengel, Bernhard Kuster, Thomas Brabletz, Luka Cicin-Sain, Ramon Arens, Andreas Vlachos, Jan Christopher Rohr, Marc Philippe Stemmler, Manfred Kopf, Zsolt Ruzsics, Philipp Henneke
Summary: The study revealed that CMV infection induces significant transformations in macrophages, giving them features of stemness, altered migration, enhanced invasiveness, and provision of the cell cycle machinery for viral proliferation. In pulmonary infection, CMV primarily targets and reprograms alveolar macrophages, changing lung physiology and facilitating bacterial infections.
Article
Biochemistry & Molecular Biology
Martin Prescher, Michele Bonus, Jan Stindt, Verena Keitel-Anselmino, Sander H. J. Smits, Holger Gohlke, Lutz Schmitt
Summary: ABCB4 is an ATP-binding cassette transporter that mainly transports lipids of the phosphatidylcholine family and a subset of multidrug-resistance-associated drugs. It shares a high degree of amino acid identity with ABCB1, leading to overlapping substrates. There are two distinct and autonomous substrate binding sites in ABCB4.
Article
Medicine, General & Internal
Stephanie Vollmer-Raschdorf, Jassin Rashidi-Alavijeh, Sebastian Voigt, Hartmut Hengel, Benjamin Borchardt, Daniela Huzly, Eva-Maria Huessler, Juergen In Der Schmitten, Anne Halenius, Katharina Willuweit, Suzan Botzenhardt, Mirko Trilling, Tobias Boettler, Dorothea Dehnen
Summary: This study aims to investigate the immune responses to the Shingrix vaccine in different patient populations and compare their vaccine reactions. The study will collect blood samples from 308 patients at seven different time points and analyze varicella zoster virus (VZV) and glycoprotein E (gE)-specific IgG and T cell responses. The primary outcome is to measure and compare the vaccine responses based on the type and degree of immunosuppression using antibody detection assays. Secondary outcomes include comparing the CD4(+) T cell responses and the severity of vaccination reactions among the three patient cohorts. The study also aims to find a potential association between VZV immune responses and clinical protection against shingles.
Article
Gastroenterology & Hepatology
Nils Bardeck, Martha Paluschinski, Mirco Castoldi, Claus Kordes, Boris Goerg, Jan Stindt, Tom Luedde, Stephan Vom Dahl, Dieter Haeussinger, David Schoeler
Summary: This study identified microRNA 141-3p as an osmosensitive miRNA that inhibits proliferation during liver cell swelling. Upregulation of microRNA 141-3p, controlled by Src-, Erk-, and p38-MAPK signaling, results in decreased mRNA levels of various genes involved in metabolic processes, macromolecular biosynthesis, and cell cycle progression.
Letter
Gastroenterology & Hepatology
Jonas Schumacher, Toni Herta, Jan Stindt, Verena Keitel, Thomas Berg