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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2434-2441. Prepublished online as a Blood First Edition Paper on October 30, 2008; DOI 10.1182/blood-2008-05-156836. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-05-156836v1 113/11/2434    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 Brodin, P. Articles by Höglund, P. Search for Related Content PubMed PubMed Citation Articles by Brodin, P. Articles by Höglund, P. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells Petter Brodin1, Tadepally Lakshmikanth1, Sofia Johansson1, Klas Kärre1, and Petter Höglund1 1 Department of Microbiology, Tumor and Cell Biology, Strategic Research Center for Studies of Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I. If self-MHC is down-regulated or absent, lack of inhibition triggers "missing self" killing. NK cells developing in the absence of MHC class I are hypo-responsive, demonstrating that MHC class I molecules are required for NK-cell education. Here, we show that the number and the type of MHC class I alleles that are present during NK-cell education quantitatively determine the frequency of responding NK cells, the number of effector functions in individual NK cells, and the amount of interferon- production in NK cells of specific Ly49 subsets. A relationship between the extent of inhibitory signals during education and functional responsiveness was corroborated by an enhanced probability of NK cells expressing more than one inhibitory receptor for a single host self–MHC class I allele to degranulate after activation. Our data suggest that the capacity of an individual NK cell to respond to stimulation is quantitatively controlled by the extent of inhibitory signals that are received from MHC class I molecules during NK-cell education. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. Schwarer Killer Ig-Like Receptor Ligand Mismatch Directs NK Cell Expansion In Vitro J. Immunol., October 1, 2009; 183(7): 4502 - 4508. [Abstract] [Full Text] [PDF] C. Sola, P. Andre, C. Lemmers, N. Fuseri, C. Bonnafous, M. Blery, N. R. Wagtmann, F. Romagne, E. Vivier, and S. Ugolini Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo PNAS, August 4, 2009; 106(31): 12879 - 12884. [Abstract] [Full Text] [PDF] S. Andersson, C. Fauriat, J.-A. Malmberg, H.-G. Ljunggren, and K.-J. Malmberg KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression Blood, July 2, 2009; 114(1): 95 - 104. [Abstract] [Full Text] [PDF]

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