Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression.
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.
Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908.|Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
Joseph S
JS
Dolina
Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908.
Sylvia
0000-0001-7631-7707
S
Cechova
Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908.
Christine K
0000-0003-1144-5104
CK
Rudy
Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908.
Sun-Sang J
0000-0001-5432-691X
SJ
Sung
Division of Inflammation Biology, Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
William W
WW
Tang
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
Joey
J
Lee
Department of Microbiology, Immunology, and Cancer Biology, Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908; and.|Department of Pathology, University of Virginia, Charlottesville, VA 22908.
Young S
0000-0002-2698-9844
YS
Hahn
Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908; thl4t@virginia.edu.
Thu H
TH
Le
D000208:Acute Disease; D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D045142:Cross-Priming; D005110:Extracellular Space / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012995:Solubility; D018183:Transplantation Chimera
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; C504407:Tmem27 protein, mouse