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

Abstract

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.