TROPHOBLAST CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) PRODUCTS ARE RESISTANT TO RAPID DEGRADATION IMPOSED BY THE HUMAN CYTOMEGALOVIRUS(HCMV) GENE-PRODUCTS US2 AND US11

US11 and US2 encode gene products expressed early in the replicative c ycle of human cytomegalovirus (HCMV), which cause dislocation of human and murine major histocompatibility complex (MHC) class I molecules f rom the lumen of the endoplasmic reticulum to the cytosol, where the c lass I heavy chains are rapidly degraded. Human histocompatibility leu kocyte antigens (HLA)-C and HLA-G are uniquely resistant to the effect s of both US11 and US2 in a human trophoblast cell line as well as in porcine endothelial cells stably transfected with human class I genes. Dislocation and degradation of MHC class I heavy chains do not appear to involve cell type-specific factors, as US11 and US2 are fully acti ve in this xenogeneic model. Importantly, trophoblasts HLA-G and HLA-C possess unique characteristics that allow their escape from HCMV-asso ciated MHC class I degradation. Trophoblast class I molecules could se rve not only to block recognition by natural killer cells, but also to guide virus-specific HLA-C- and possibly HLA-G-restricted cytotoxic T -lymphocytes to their targets.