SUSCEPTIBILITY TO NATURAL-KILLER-CELLS AND DOWN-REGULATION OF MHC CLASS-I EXPRESSION IN ADENOVIRUS-12 TRANSFORMED-CELLS ARE REGULATED BY DIFFERENT E1A DOMAINS

All human adenoviruses transform rodent cells in vitro, but only cells transformed by serotypes belonging to subgroups A (Ad12) and B (Ad3) are tumorigenic for immunocompetent animals. In these cells, the expre ssion of MHC-class I antigens is repressed and might allow them to esc ape from recognition by cytotoxic T lymphocytes (CTL) and to develop i n tumor. Furthermore, these cell lines appear resistant to lysis by na tural killer (NK) cells. To determine the E1A domain(s) responsible fo r these properties several cell lines were created by transforming bab y rat kidney (BRK) cells with a set of plasmids expressing different A d2/Ad12 hybrid E1A gene products. The MHC class I gene expression was inhibited in cells expressing the Ad12 13S mRNA product and in cells t ransformed with Ad2/Ad12 hybrid E1A gene product harboring the C-termi nal part of the conserved region (CR) 3 of Ad12. Susceptibility of the se transformed cell lines to NK cells was determined by cytolytic assa ys. The results obtained suggest that two Ad12 E1A domains are require d to induce resistance of the cell lines to NK cells.