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The E3 19,000-dalton protein termed "E3/19K" of adenovirus type 2 binds to human class I histocompatibility antigens (HLA antigens). Human 293.12 cultured cells that express a cloned gene for the E3/19K protein show reduced levels of HLA antigens on the cell surface compared to parental 293 cells. We have transfected these cell lines with plasmid DNA containing the murine histocompatibility H-2Kd allele to demonstrate that this antigen binds also to the E3/19K protein. The resulting association prevents the H-2Kd antigen from being terminally glycosylated and inhibits its cell-surface expression. Two murine cytolytic T-lymphocyte clones specific for HLA antigens and restricted by the H-2Kd antigen lyse the human 293Kd cells. In the presence of the E3/19K protein, a dramatically reduced cell surface density of both HLA and H-2Kd antigens was shown. This decreased amount of cell-surface HLA/H-2Kd antigens correlated with a reduction in susceptibility to lysis of the target cells. In particular, the cell-surface level of the H-2Kd antigen, which is the restricting element, was crucial for efficient lysis. Thus, the E3/19K protein of adenovirus type 2 indirectly reduces the cellular immune recognition in the in vitro system. This might be the mechanism involved in latent and persistent infections caused by adenoviruses in vivo.

proceedings of the national academy of sciences of the united states of america

"E3/19K" protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens.