期刊
JOURNAL OF IMMUNOLOGY
卷 198, 期 6, 页码 2341-2351出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1502234
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资金
- Department of Medicine at University of Virginia
Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8(+) T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8(+) T cells within the liver microenvironment. Processing of soluble and cell-associated Ags into peptide displayed byMHC I is however defective in hepatocytes lacking collectrin, an intracellular chaperone protein that localizes within the endoplasmic reticulum-Golgi intermediate compartment. Loss of hepatic collectrin expression leads to the diminished cross-priming and expansion of cytolytic antiviral CD8(+) T cells. This study demonstrates that collectrin positively regulates processing of engulfed Ags into MHC I: peptide complexes within hepatocytes. Collectrin-mediated cross-presentation supports intrahepatic adaptive antiviral immune responses and may lead to insights into the nature of how the liver acts as a primary site of CD8(+) T cell activation.
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