HCMV glycoprotein US6 mediated inhibition of TAP does not affect HLA-E dependent protection of K-562 cells from NK cell lysis

• Published in: Human immunology Vol. 64; no. 2; pp. 231 - 237
• Main Authors: Ulbrecht, Matthias, Hofmeister, Valeska, Yüksekdag, Gülnihål, Ellwart, Joachim W, Hengel, Hartmut, Momburg, Frank, Martinozzi, Silvia, Reboul, Murielle, Pla, Marika, Weiss, Elisabeth H
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2003
• Subjects: Animals; Antigen Presentation; Antigens, CD - immunology; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP-Binding Cassette Transporters - antagonists & inhibitors; Cytotoxicity, Immunologic; Gene Expression Regulation; Genes, MHC Class I; Histocompatibility Antigens Class I - immunology; HLA Antigens - biosynthesis; HLA Antigens - immunology; HLA-A2 Antigen - chemistry; HLA-A2 Antigen - immunology; HLA-E; HLA-E Antigens; human cytomegalovirus; Humans; K562 Cells; Killer Cells, Natural - immunology; killer inhibitory receptor; Lectins, C-Type - immunology; Lymphocyte Activation; MHC class I; Mice; NK cell; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily D; Peptide Fragments - immunology; Peptide Fragments - metabolism; Receptors, Immunologic - immunology; Receptors, Natural Killer Cell; Recombinant Fusion Proteins - immunology; RNA-Binding Proteins - physiology; Transfection; Viral Proteins - physiology; MHC class I; killer inhibitory receptor; human cytomegalovirus; NK cell; HLA-E
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(02)00788-7

Human cytomegalovirus has evolved multiple strategies to interfere with immune recognition by the host. A variety of mechanisms affect antigen presentation by major histocompatibility complex class I molecules resulting in a reduced class I cell-surface expression. This downregulation is expected to trigger natural killer (NK) cytotoxicity, requiring counteraction by the virus to establish long-term infection. Here we describe that the human cytomegalovirus gpUS6 protein, which has been demonstrated to downregulate the expression of human leukocyte antigen (HLA) class I and the presentation of cytotoxic T lymphocyte epitopes by blocking transporter associated with antigen presentation (TAP function), does not affect the ability of HLA-E to inhibit NK cell mediated lysis of K-562 cells by interaction with CD94/NKG2A expressed on NK cells. Cell surface expression and function of HLA-E is not altered although gpUS6 inhibits TAP-dependent peptide transport by 95%. Moreover, HLA-E molecules presenting HLA class I signal sequence-derived peptides are functionally detectable on transfected TAP-deficient RMA-S cells.