DOWN-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION AND SUSCEPTIBILITY TO NATURAL-KILLER-CELLS IN CELLS TRANSFORMED WITHTHE ONCOGENIC ADENOVIRUS-12 ARE REGULATED BY DIFFERENT E1A DOMAINS

All adenoviruses transform rodent cells in vitro, but only cells trans formed by serotypes belonging to subgroups A (Ad12) and B (Ad3) are tu morigenic for immunocompetent animals. In these cells, the expression of major histocompatibility complex (MHC) class I antigens is represse d and might allow them to escape from recognition by cytotoxic T lymph ocytes and to develop in tumor. Furthermore, these cell lines appear r esistant to lysis by natural killer (NK) cells. To determine the E1A d omain(s) responsible for these properties several cell Lines were crea ted by transforming baby rat kidney cells with a set of plasmids expre ssing different Ad2/Ad12 hybrid E1A gene products. ?he class 1 gene ex pression was inhibited in cells expressing the Ad12 13S mRNA product a nd in cells transformed with Ad2/Ad12 hybrid E1A gene product harborin g the C-terminal part of. the conserved region (CR) 3 of Ad12. Suscept ibility of these transformed cell lines to NK cells was determined by cytolytic assays. The results obtained suggest that two of Ad12 E1A do mains are required to induce resistance of the cell lines to NX cells.