Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression

Abstract

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 by MHC 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.