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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2003-01-0019. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0019v1 102/4/1389    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Salih, H. R. Articles by Steinle, A. Search for Related Content PubMed PubMed Citation Articles by Salih, H. R. Articles by Steinle, A. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1389-1396 IMMUNOBIOLOGY Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia Helmut Rainer Salih, Holger Antropius, Friederike Gieseke, Stefan Zoltan Lutz, Lothar Kanz, Hans-Georg Rammensee, and Alexander Steinle From the Department of Internal Medicine II, University Hospital, Eberhard-Karls-University, Tübingen, Germany; and Department of Immunology, Eberhard-Karls-University, Tübingen, Germany 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. 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