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The interactions between CD8<jats:sup>+<\/jats:sup>T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen\u2010derived peptides along with costimulatory receptor\/ligand stimuli. Thus, to escape from CD8<jats:sup>+<\/jats:sup>T\u2010cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and\/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell\u2010mediated lysis could be abrogated by the expression of inhibiting NK cell receptors. This review discusses the molecular mechanisms utilized by viruses to inhibit the formation, transport and\/or expression of HLA class I antigen\/peptide complexes on the cell surface. 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