Major histocompatibility complex (MHC) class I molecules associate with a variety of peptide ligands during biosynthesis and present these ligands on the cell surface for recognition by cytotoxic T cells. We have designed conditional MHC ligands that form stable complexes with MHC molecules but degrade on command, by exposure to a defined photostimulus. 'Empty MHC molecules' generated in this manner can be loaded with arrays of peptide ligands to determine MHC binding properties and to monitor antigen-specific T-cell responses in a high-throughput manner. We document the value of this approach by identifying cytotoxic T-cell epitopes within the H5N1 influenza A/Vietnam/1194/04 genome.
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http://dx.doi.org/10.1038/nm1360 | DOI Listing |
Unlabelled: Regulatory T cells (T cells) play a critical role in suppressing anti-tumor immunity, often resulting in unfavorable clinical outcomes across numerous cancers. However, systemic T depletion, while augmenting anti-tumor responses, also triggers detrimental autoimmune disorders. Thus, dissecting the mechanisms by which T cells navigate and exert their functions within the tumor microenvironment (TME) is pivotal for devising innovative T -centric cancer therapies.
View Article and Find Full Text PDFJ Allergy Clin Immunol
December 2024
Department of Medicine, Gastroenterology and Hepatology Division, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:
Background: Eosinophilic esophagitis (EoE) is a chronic T2-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood.
Objective: We investigated the role of epithelial IKKβ/NF-κB signaling in EoE pathogenesis using a mouse model with conditional Ikkβ knockout in esophageal epithelial cells (Ikkβ).
Scand J Prim Health Care
November 2024
Department of Public Health and Nursing, NTNU, Trondheim, Norway.
Objective: This study examines the experiences of clinical encounters with young unaccompanied refugees in Norway and Denmark among both general practitioners (GPs) and physicians in migrant health clinics (MHC physicians), and it identifies important aspects that should be taken into consideration for improving the quality of healthcare for these patients.
Methodology: Ten individual in-depth interviews with physicians in Norway and Denmark were conducted and analysed using interpretative phenomenology. Axel Honneth's theory of recognition was our theoretical lens.
Lab Invest
November 2024
Department of Dermatology, Johns Hopkins University, Baltimore, Maryland; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; The Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland. Electronic address:
Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a poor prognosis. One of the major mechanisms of immune evasion in MCC involves downregulation of major histocompatibility complex class I (MHC-I). Anti-PD-1/programmed death ligand 1 checkpoint inhibitors have revolutionized treatment for MCC, producing objective responses in approximately 50% of patients, and are now the standard of care; however, a substantial proportion of patients either fail to respond or develop resistance to checkpoint inhibitors.
View Article and Find Full Text PDFCell Death Dis
October 2024
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Sirtuin 1 (SIRT1) is a class III histone deacetylase (HDAC3) that plays a crucial role in regulating the activation and differentiation of dendritic cells (DCs) as well as controlling the polarization and activation of T cells. Obesity, a chronic inflammatory condition, is characterized by the activation of immune cells in various tissues. We hypothesized that SIRT1 might influence the phenotype and functions of DCs through the Ido1 pathway, ultimately leading to the polarization towards pro-inflammatory T cells in obesity.
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