Cutting Edge: The Human Cytomegalovirus UL40 Gene Product Contains a Ligand for HLA-E and Prevents NK Cell-Mediated Lysis

Human CMV has evolved multiple strategies to interfere with immune recognition of the host. A variety of mechanisms target Ag presentation by MHC class I molecules resulting in a reduced class I cell-surface expression. This down-regulation of class I molecules is expected to trigger NK cytotoxicity...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2000-05, Vol.164 (10), p.5019-5022
Main Authors: Ulbrecht, Matthias, Martinozzi, Silvia, Grzeschik, Mariola, Hengel, Hartmut, Ellwart, Joachim W, Pla, Marika, Weiss, Elisabeth H
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibodies, Monoclonal - metabolism
Cells, Cultured
Cytomegalovirus - immunology
Cytotoxicity, Immunologic - immunology
Fibroblasts - immunology
Fibroblasts - metabolism
Fibroblasts - virology
Histocompatibility Antigens Class I - metabolism
HLA Antigens - metabolism
HLA-E Antigens
Humans
Immunosuppressive Agents - pharmacology
K562 Cells
Killer Cells, Natural - immunology
Ligands
Molecular Sequence Data
Oligopeptides
Open Reading Frames - immunology
Peptide Fragments - immunology
Peptide Fragments - isolation & purification
Peptides - immunology
Protein Processing, Post-Translational - immunology
Transfection
Viral Proteins - genetics
Viral Proteins - immunology
Viral Proteins - metabolism
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Summary:Human CMV has evolved multiple strategies to interfere with immune recognition of the host. A variety of mechanisms target Ag presentation by MHC class I molecules resulting in a reduced class I cell-surface expression. This down-regulation of class I molecules is expected to trigger NK cytotoxicity, which would have to be counteracted by the virus to establish long-term infection. Here we describe that the human CMV open reading frame UL40 encodes a canonical ligand for HLA-E, identical with the HLA-Cw03 signal sequence-derived peptide. Expression of UL40 in HLA-E-positive target cells conferred resistance to NK cell lysis via the CD94/NKG2A receptor. Generation of the UL40-derived HLA-E ligand was also observed in TAP-deficient cells. The presence of a functional TAP-independent HLA-E ligand in the UL40 signal sequence implicates this viral gene as an important negative regulator of NK activity.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.164.10.5019