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.

Chen M, Tabaczewski P, Truscott SM, Van Kaer L, Stroynowski I
J Immunol. 2005 175 (2): 1047-55

PMID: 16002705 · DOI:10.4049/jimmunol.175.2.1047

Hepatic expression levels of class I MHC 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 K(b) and D(b) on C57BL/6 mouse hepatocytes are nearly as high as on splenocytes, as are the lysate concentrations of mRNA encoding H chain and beta(2)-microglobulin (beta(2)m). In contrast, the components of the peptide-loading pathway are reduced in hepatocytes. Despite the difference in the stoichiometric ratios of H chain/beta(2)m/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-gamma 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 beta(2)m 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.

MeSH Terms (26)

Animals Antigen Presentation Antiporters ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP Binding Cassette Transporter, Subfamily B, Member 3 Cell Membrane Cells, Cultured Cysteine Endopeptidases Gene Expression Regulation H-2 Antigens Hepatocytes Histocompatibility Antigen H-2D Immunoglobulins Listeriosis Male Membrane Transport Proteins Mice Mice, Inbred C57BL Mice, Knockout Multienzyme Complexes Proteasome Endopeptidase Complex Protein Processing, Post-Translational Protein Subunits Signal Transduction Spleen

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