Science · 2000 · 664 citations · 27 references
Life SciencesImmunologyInfectious DiseasesCellular ImmunologyInnate ImmunityMolecular ImmunologyAntigen PresentationAntigen ProcessingHistocompatibility AntigensMajor Histocompatibility ComplexNatural Killer Cell BiologyNatural Killer Cell RegulationCell LysisClassical Mhc MoleculesConserved AntigensHla Antigen ExpressionHla Expression LevelsMhc Class I MoleculesMhc Escape MechanismsNatural Killer Cell Inhibitory Signaling
HLA‑E, a nonclassical MHC class I molecule that inhibits NK‑cell lysis via CD94/NKG2A, is expressed on the cell surface when bound to conserved peptides—including those from the HCMV UL40 leader sequence—and is up‑regulated by HCMV while classical MHC I is down‑regulated. The HCMV glycoprotein UL40 up‑regulates HLA‑E on target cells independently of TAP, shielding them from NK‑cell lysis and providing a viral immune‑escape mechanism.
The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell–mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.
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HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C
Véronique M. Braud, David Allan, Christopher A. O'Callaghan et al. · Nature · 1998 · 2.2K citations