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Articles

Danny J. Schust^*, Domenico Tortorella^*, Jörg Seebach, Cindy Phan^*, and Hidde L. Ploegh^*

From the ^* Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115; and the Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts 02119

US11 and US2 encode gene products expressed early in the replicative cycle of human cytomegalovirus (HCMV), which cause dislocation of human and murine major histocompatibility complex (MHC) class I molecules from the lumen of the endoplasmic reticulum to the cytosol, where the class I heavy chains are rapidly degraded. Human histocompatibility leukocyte antigens (HLA)-C and HLA-G are uniquely resistant to the effects 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 active in this xenogeneic model. Importantly, trophoblasts HLA-G and HLA-C possess unique characteristics that allow their escape from HCMV-associated MHC class I degradation. Trophoblast class I molecules could serve 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.

Key Words: trophoblast • cytomegalovirus • human • MHC class I • HLA-G

Abbreviations used: CM, complete medium; ER, endoplasmic reticulum; HCMV, human cytomegalovirus; MOI, multiplicity of infection.

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