title: Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia.
abstract: NKG2D ligands (NKG2DLs) mark malignant cells for recognition by natural killer (NK) cells and cytotoxic T lymphocytes via the activating immunoreceptor NKG2D. This led to the hypothesis that NKG2DLs play a critical role in tumor immune surveillance. The human NKG2DLs MICA and MICB are expressed on tumors of epithelial origin in vivo. For the other recently described set of human NKG2DLs, the UL16-binding proteins (ULBPs), expression in vivo is as yet undefined. In this study we investigated expression and function of NKG2DLs in leukemia using a panel of newly generated NKG2DL-specific monoclonal antibodies. We report that leukemia cells from patients variously express MIC and ULBP molecules on the cell surface with MICA most frequently detected. Patient leukemia cells expressing MICA were lysed by NK cells in an NKG2D-dependent fashion. Sera of patients, but not of healthy donors, contained elevated levels of soluble MICA (sMICA). We also detected increased sMICB levels in patient sera using a newly established MICB-specific enzyme-linked immunosorbent assay. Reduction of leukemia MIC surface expression by shedding may impair NKG2D-mediated immune surveillance of leukemias. In addition, determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies.
authors.affiliation: Department of Internal Medicine II, University Hospital, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: Helmut Rainer
authors.initials: HR
authors.lastname: Salih
authors.forename: Holger
authors.initials: H
authors.lastname: Antropius
authors.forename: Friederike
authors.initials: F
authors.lastname: Gieseke
authors.forename: Stefan Zoltan
authors.initials: SZ
authors.lastname: Lutz
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinle
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000097:blood* / Q000276:immunology; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D008297:Male; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell