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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2028-2035. Prepublished online as a Blood First Edition Paper on November 4, 2004; DOI 10.1182/blood-2004-08-3174. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3174v1 105/5/2028    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 Draghi, M. Articles by Parham, P. Search for Related Content PubMed PubMed Citation Articles by Draghi, M. Articles by Parham, P. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I Monia Draghi, Nobuyo Yawata, Michael Gleimer, Makoto Yawata, Nicholas M. Valiante, and Peter Parham From the Departments of Structural Biology and Microbiology & Immunology, Stanford University School of Medicine, CA; and Chiron, Vaccines Research, Emeryville, CA. Natural killer (NK) cells activate quickly in response to pathogens, tumors, and allogeneic hematopoietic cell transplants. Modulating the NK cell response are clonally distributed NK cell receptors that survey cells for change in the expression of major histocompatibility complex (MHC) class I and structurally related ligands. Here the enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine staining (ICS), and short-term culture were used to quantify the response of bulk NK cell populations from human donors to HLA class I–deficient 221 cells and to 221 cells transfected with single HLA class I allotypes. NK cells in cultures containing interleukin-2 (IL-2) or IL-12 exhibited specificities of HLA class I–mediated inhibition that correlated well with those previously defined using NK cell clones in long-term culture and with the frequencies of cells expressing particular inhibitory HLA class I receptors. Culture with IL-12, but not IL-2, gave an increased frequency of cells expressing CD94: NKG2A but no change in killer immunoglobulin-like receptor (KIR) expression. For some heterozygote combinations of KIR3DL1 alleles, ICS can be used to compare the functional properties of the 2 allotypes. Thus, both the low-expressing KIR3DL1*005 and the high-expressing KIR3DL1*002 gave similar inhibitory response on challenge with an HLA-B*5801 ligand. The single-cell assays developed here should facilitate future population study and clinical analysis of human NK cell regulation by MHC class I. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. A. Foley, D. D. Santis, E. Van Beelen, L. J. Lathbury, F. T. Christiansen, and C. S. Witt The reactivity of Bw4+ HLA-B and HLA-A alleles with KIR3DL1: implications for patient and donor suitability for haploidentical stem cell transplantations Blood, July 15, 2008; 112(2): 435 - 443. [Abstract] [Full Text] [PDF] A. K. Moesta, P. J. Norman, M. Yawata, N. Yawata, M. Gleimer, and P. Parham Synergistic Polymorphism at Two Positions Distal to the Ligand-Binding Site Makes KIR2DL2 a Stronger Receptor for HLA-C Than KIR2DL3 J. 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Verneris Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells Blood, December 1, 2006; 108(12): 3824 - 3833. [Abstract] [Full Text] [PDF] M. Yawata, N. Yawata, M. Draghi, A.-M. Little, F. Partheniou, and P. Parham Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function J. Exp. Med., March 20, 2006; 203(3): 633 - 645. [Abstract] [Full Text] [PDF] C. R. Brooks, T. Elliott, P. Parham, and S. I. Khakoo The Inhibitory Receptor NKG2A Determines Lysis of Vaccinia Virus-Infected Autologous Targets by NK Cells J. Immunol., January 15, 2006; 176(2): 1141 - 1147. [Abstract] [Full Text] [PDF]

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