Class I molecules retained in the endoplasmic reticulum bind antigenic peptides

doi:10.1084/jem.177.6.1633

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Class I molecules retained in the endoplasmic reticulum bind antigenic peptides

CK Lapham, I Bacik, JW Yewdell, KP Kane and JR Bennink
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.

We isolated major histocompatibility complex (MHC)-specific viral peptides from cells infected with influenza virus in the continuous presence of the drug brefeldin A, which blocks exocytosis of newly synthesized MHC class I molecules. MHC-specific peptides were also isolated from cells expressing mouse Kd class I MHC molecules whose cytoplasmic domain was substituted by that of the adenovirus E3/19K glycoprotein. This molecule was retained in an intracellular pre-Golgi complex compartment as demonstrated by immunocytochemical and biochemical means. Since we show that intracellular association of antigenic peptides with such retained class I molecules is necessary for their isolation from cellular extracts, this provides direct evidence that naturally processed peptides associate with class I MHC molecules in an early intracellular exocytic compartment.
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