T cells are activated by fragments of antigenic proteins bound to major histocompatibility complex (MHC) molecules and displayed on the cell surface. MHC class II proteins scavenge processed protein antigens from within endosomal compartments. The antigenic peptides are generated within these and other intracellular compartments using the array of proteolytic enzymes normally involved in terminal protein degradation. Antigen-presenting cells use different mechanisms to exploit and control the activity of these enzymes so as to ensure the generation of a wide variety of peptides, while preventing the destruction of antigenic epitopes by excessive proteolysis.
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http://dx.doi.org/10.1016/s0968-0004(97)01116-x | DOI Listing |
Microbiol Spectr
January 2025
Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NHCl), indicating entry via the endocytosis route.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Department of Genetics, Yale School of Medicine, USA.
Retromer mediates retrograde transport of protein cargos from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pathology, Division of Microbiology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375, Wroclaw, Poland.
The process of viral entry into host cells is crucial for the establishment of infection and the determination of viral pathogenicity. A comprehensive understanding of entry pathways is fundamental for the development of novel therapeutic strategies. Standard techniques for investigating viral entry include confocal microscopy and flow cytometry, both of which provide complementary qualitative and quantitative data.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Experimental Medicine, University of Salento, Via Provinciale Lecce-Monteroni n. 165, 73100 Lecce, Italy.
Peripherin belongs to heterogeneous class III of intermediate filaments, and it is the only intermediate filament protein selectively expressed in the neurons of the peripheral nervous system. It has been previously discovered that peripherin interacts with proteins important for the endo-lysosomal system and for the transport to late endosomes and lysosomes, such as RAB7A and AP-3, although little is known about its role in the endocytic pathway. Here, we show that peripherin silencing affects lysosomal abundance but also positioning, causing the redistribution of lysosomes from the perinuclear area to the cell periphery.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis.
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