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* Center for Immunology,
Department of Internal Medicine, and
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and ¶ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
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 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
2-microglobulin (
2m). In contrast, the components of the peptide-loading pathway are reduced in hepatocytes. Despite the difference in the stoichiometric ratios of H chain/
2m/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-
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
2m 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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