Class I molecules retained in the endoplasmic reticulum bind antigenic peptides.
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.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
C K
CK
Lapham
I
I
Bacík
J W
JW
Yewdell
K P
KP
Kane
J R
JR
Bennink
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism*; D020126:Brefeldin A; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins / Q000378:metabolism
D000956:Antigens, Viral; D003517:Cyclopentanes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D015395:Histocompatibility Antigens Class I; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D020126:Brefeldin A