DOWN-REGULATION OF MHC CLASS-I EXPRESSION DUE TO INTERFERENCE WITH P105-NF-KAPPA-B1 PROCESSING BY AD12E1A

We have previously demonstrated that expression of major histocompatib ility complex (MHC) class I genes is repressed in baby rat kidney cell s transformed by early region 1 of oncogenic adenovirus type 12 (Ad12E 1). Reduced expression of MHC class I antigens contributes to the esca pe of Ad12-transformed cells from T-cell-mediated immune surveillance and to tumour induction. In this study, we show that repression of MHC class I expression by Ad12E1A is mediated via the N2TF1 element of th e MHC class I promoter. This element binds NF kappa B and KBF1, two fa ctors which play a major role in the regulation of MHC class I express ion in vivo. In extracts from Ad12E1-transformed cells, binding of KBF 1 and NF kappa B to the H2TF1 element is decreased. This is caused by reduced production of p50-NF kappa B1, the 50 kDa subunit shared by KB F1 and NF kappa B, due to interference with p105-NF kappa B1 processin g by Ad12-13S-E1A protein. Overexpression of the p105-NF kappa B1 cDNA , or of a truncated p105-NF kappa B1 cDNA that codes for p50-NF kappa B1, restores MHC class I expression in Ad12E1-transformed cells. These data demonstrate that downregulation of MHC class I expression in Ad1 2E1-transformed cells is due to interference with processing of p105-N F kappa B1 by the Ad12-13S-E1A protein.