PMID- 12559625 OWN - NLM STAT- MEDLINE DCOM- 20030926 LR - 20231213 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 64 IP - 2 DP - 2003 Feb TI - HCMV glycoprotein US6 mediated inhibition of TAP does not affect HLA-E dependent protection of K-562 cells from NK cell lysis. PG - 231-7 AB - 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. FAU - Ulbrecht, Matthias AU - Ulbrecht M AD - Department Biologie II, Ludwig-Maximilians-Universitat Munchen, Anthropologie und Humangenetik, Munich, Germany. FAU - Hofmeister, Valeska AU - Hofmeister V FAU - Yuksekdag, Gulnihal AU - Yuksekdag G FAU - Ellwart, Joachim W AU - Ellwart JW FAU - Hengel, Hartmut AU - Hengel H FAU - Momburg, Frank AU - Momburg F FAU - Martinozzi, Silvia AU - Martinozzi S FAU - Reboul, Murielle AU - Reboul M FAU - Pla, Marika AU - Pla M FAU - Weiss, Elisabeth H AU - Weiss EH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antigens, CD) RN - 0 (HLA Antigens) RN - 0 (HLA-A2 Antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (KLRC1 protein, human) RN - 0 (KLRD1 protein, human) RN - 0 (Klrc1 protein, mouse) RN - 0 (Klrd1 protein, mouse) RN - 0 (Lectins, C-Type) RN - 0 (NK Cell Lectin-Like Receptor Subfamily C) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (Peptide Fragments) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Natural Killer Cell) RN - 0 (Recombinant Fusion Proteins) RN - 0 (TAP1 protein, human) RN - 0 (Tap1 protein, mouse) RN - 0 (US6 protein, Human cytomegalovirus) RN - 0 (Viral Proteins) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 2 MH - ATP-Binding Cassette Transporters/*antagonists & inhibitors MH - Animals MH - Antigen Presentation MH - Antigens, CD/immunology MH - Cytotoxicity, Immunologic MH - Gene Expression Regulation MH - Genes, MHC Class I MH - HLA Antigens/biosynthesis/*immunology MH - HLA-A2 Antigen/chemistry/immunology MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - K562 Cells MH - Killer Cells, Natural/*immunology MH - Lectins, C-Type/immunology MH - Lymphocyte Activation MH - Mice MH - NK Cell Lectin-Like Receptor Subfamily C MH - NK Cell Lectin-Like Receptor Subfamily D MH - Peptide Fragments/immunology/metabolism MH - RNA-Binding Proteins/*physiology MH - Receptors, Immunologic/immunology MH - Receptors, Natural Killer Cell MH - Recombinant Fusion Proteins/immunology MH - Transfection MH - Viral Proteins/*physiology MH - HLA-E Antigens EDAT- 2003/02/01 04:00 MHDA- 2003/09/27 05:00 CRDT- 2003/02/01 04:00 PHST- 2003/02/01 04:00 [pubmed] PHST- 2003/09/27 05:00 [medline] PHST- 2003/02/01 04:00 [entrez] AID - S0198885902007887 [pii] AID - 10.1016/s0198-8859(02)00788-7 [doi] PST - ppublish SO - Hum Immunol. 2003 Feb;64(2):231-7. doi: 10.1016/s0198-8859(02)00788-7.