Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight polypeptide proteasome subunit components of antigen processing and presentation pathway

Ming Chen, Piotr Tabaczewski, Steven M. Truscott, Luc Van Kaer, Iwona Stroynowski

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Hepatic expression levels of class IMHC Ags are generally regarded as very low. Because the status of these Ags and their ability to present peptides are important for the understanding of pathogen clearance and tolerogenic properties of the liver, we set out to identify the factors contributing to the reported phenotype. Unexpectedly, we found that the surface densities of Kb and Db on C57BL/6 mouse hepatocytes are nearly as high as on splenocytes, as are the lysate concentrations of mRNA encoding H chain and β2-microglobulin (β2m). In contrast, the components of the peptide-loading pathway are reduced in hepatocytes. Despite the difference in the stoichiometric ratios of H chain/β2m/ peptide-loading machineries, both cell types express predominantly thermostable class I and are critically dependent on TAP and tapasin for display of surface Ags. Minor differences in the expression patterns in tapasin-/- background suggest cell specificity in class I assembly. Under immunostimulatory conditions, such as exposure to IFN-γ or Listeria monocytogenes, hepatocytes respond with a vigorous mRNA synthesis of the components of the Ag presentation pathway (up to 10-fold enhancement) but up-regulate H chain and β2m to a lesser degree (<2-fold). This type of response should promote rapid influx of newly generated peptides into the endoplasmic reticulum and preferential presentation of foreign/induced Ag by hepatic class I.

Original languageEnglish (US)
Pages (from-to)1047-1055
Number of pages9
JournalJournal of Immunology
Volume175
Issue number2
StatePublished - Jul 15 2005

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Antigen Presentation
Proteasome Endopeptidase Complex
Hepatocytes
Molecular Weight
Peptides
Liver
Messenger RNA
Listeria monocytogenes
Inbred C57BL Mouse
Endoplasmic Reticulum
Up-Regulation
Phenotype
tapasin

ASJC Scopus subject areas

  • Immunology

Cite this

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abstract = "Hepatic expression levels of class IMHC Ags are generally regarded as very low. Because the status of these Ags and their ability to present peptides are important for the understanding of pathogen clearance and tolerogenic properties of the liver, we set out to identify the factors contributing to the reported phenotype. Unexpectedly, we found that the surface densities of Kb and Db on C57BL/6 mouse hepatocytes are nearly as high as on splenocytes, as are the lysate concentrations of mRNA encoding H chain and β2-microglobulin (β2m). In contrast, the components of the peptide-loading pathway are reduced in hepatocytes. Despite the difference in the stoichiometric ratios of H chain/β2m/ peptide-loading machineries, both cell types express predominantly thermostable class I and are critically dependent on TAP and tapasin for display of surface Ags. Minor differences in the expression patterns in tapasin-/- background suggest cell specificity in class I assembly. Under immunostimulatory conditions, such as exposure to IFN-γ or Listeria monocytogenes, hepatocytes respond with a vigorous mRNA synthesis of the components of the Ag presentation pathway (up to 10-fold enhancement) but up-regulate H chain and β2m to a lesser degree (<2-fold). This type of response should promote rapid influx of newly generated peptides into the endoplasmic reticulum and preferential presentation of foreign/induced Ag by hepatic class I.",
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AU - Tabaczewski, Piotr

AU - Truscott, Steven M.

AU - Van Kaer, Luc

AU - Stroynowski, Iwona

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