Antigen Presentation Requires Transport of MHC Class I Molecules from the Endoplasmic Reticulum

The role of exocytosis of major histocompatibility complex (MHC) class I molecules in the presentation of antigens to mouse cytotoxic T lymphocytes (CTLs) was examined by use of a recombinant vaccinia virus that expresses the E19 glycoprotein from adenovirus. E19 blocked the presentation of vaccinia and influenza virus proteins to CTLs in a MHC class I allele-specific manner identical to its inhibition of MHC class I transport from the endoplasmic reticulum. This finding indicates that (i) the relevant parameter for antigen presentation is the rate of MHC class I molecule exocytosis, not the level of class I cell surface expression, and (ii) association of class I molecules with antigen is likely to occur within the endoplasmic reticulum.