RETENTION OF ADENOVIRUS-E19 GLYCOPROTEIN IN THE ENDOPLASMIC-RETICULUM IS ESSENTIAL TO ITS ABILITY TO BLOCK ANTIGEN PRESENTATION

The E3/19K glycoprotein of adenovirus functions to diminish recognition of adenovirus-infected cells by major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) by binding intracellular class I molecules and preventing them from reaching the plasma membrane. In the present study we have characterized the nature of the interaction between E3/19K and the H-2K(d) (K(d)) molecule. An E3/19K molecule genetically engineered to terminate six residues from its normal COOH terminus (DELTA-E19), was found to associate with K(d) in a manner indistinguishable from wild-type E3/19K. Unlike E3/19K, however, DELTA-E19 was transported through the Golgi complex to the plasma membrane, where it could be detected biochemically and immunocytochemically using a monoclonal antibody specific for the lumenal domain of E3/19K. Importantly, DELTA-E19 also differed from E3/19K in being unable to prevent the presentation of K(d)-restricted viral proteins to CTLs. This is unlikely to be due to DELTA-E19 having a lower avidity for K(d) than E3/19K, since DELTA-E19 was able to compete with E3/19K for K(d) binding, both physically, and functionally in nullifying the E3/19K blockade of antigen presentation. These findings indicate that the ability of E3/19K to block antigen presentation is due solely to its ability to retain newly synthesized class I molecules in the endoplasmic reticulum.