Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40

The nonclassical major histocompatibility complex (MHC) class I molecule HL A-E inhibits natural killer (NK) cell-mediated lysis by interacting with CD 94/ NKG2A receptors. Surface expression of HLA-E depends on binding of cons erved peptides derived from MHC class I molecules. The same peptide is pres ent in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associat ed with antigen processing, gpUL40 can up-regulate expression of HLA-E, whi ch protects targets from NK cell Lysis. While classical MHC class I molecul es are down-regulated, HLA-E is up-regulated by HCMV. induction of HLA-E su rface expression by gpUL40 may represent an escape route for HCMV.