The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/ II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
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http://dx.doi.org/10.1007/s003830050746 | DOI Listing |
FASEB J
January 2025
Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe liver inflammation and fibrosis due to an imbalanced immune response caused by enhanced bacterial components. The progression of MASH is closely linked to increased permeability of intestinal mucosal barrier facilitating enter of bacterial components into hepatic portal venous system. B cells are important immune cells for adaptive responses and enhance hepatic inflammation through cytokine production and T cell activation.
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Department of Dermatology and Allergy, University Hospital of Munich, Ludwig-Maximilian-University, Munich, Germany.
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View Article and Find Full Text PDFCancer Immunol Res
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Vanderbilt University, Nashville, TN, United States.
Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry.
View Article and Find Full Text PDFBiomaterials
January 2025
Department of Biomedical Engineering, University of Iowa, Iowa City, IA, 52242, USA; Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USA. Electronic address:
Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA.
The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.
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