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Science 11 February 2000:
Vol. 287. no. 5455, pp. 1031 - 1033
DOI: 10.1126/science.287.5455.1031
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Surface Expression of HLA-E, an Inhibitor of Natural Killer Cells, Enhanced by Human Cytomegalovirus gpUL40

Peter Tomasec, 1* Veronique M. Braud, 2*dagger Carole Rickards, 1 Martin B. Powell, 1 Brian P. McSharry, 1 Stephan Gadola, 2 Vincenzo Cerundolo, 2 Leszek K. Borysiewicz, 1 Andrew J. McMichael, 2 Gavin W. G. Wilkinson 1

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.

1 Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK.
2 Medical Research Council Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: vbraud{at}molbiol.ox.ac.uk

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