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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4449-4457. Prepublished online as a Blood First Edition Paper on February 9, 2006; DOI 10.1182/blood-2005-06-2519. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-06-2519v1 107/11/4449    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 Henel, G. Articles by Goronzy, J. J. Search for Related Content PubMed PubMed Citation Articles by Henel, G. Articles by Goronzy, J. J. Related Collections Immunobiology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Uncoupling of T-cell effector functions by inhibitory killer immunoglobulin–like receptors Gabriella Henel, Karnail Singh, Dapeng Cui, Sergey Pryshchep, Won-Woo Lee, Cornelia M. Weyand, and Jörg J. Goronzy From the Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University, Atlanta, GA; and the Department of Immunology, Mayo Graduate School, Rochester, MN. Killer immunoglobulin–like receptors (KIRs) are a family of regulatory cell-surface molecules expressed on natural killer (NK) cells and memory T-cell subsets. Their ability to prevent the formation of an activation platform and to inhibit NK cell activation is the basis of the missing self model of NK cell function. The benefits of KIR expression for T-cell biology are unclear. We studied how KIR2DL2 regulates T-cell function. Engagement of KIR2DL2 by the ligand human leukocyte antigen (HLA)–Cw3 did not affect conjugate formation between CD4+KIR2DL2+ T cells and superantigen-pulsed target cells or the development of mature immune synapses with lipid rafts. KIR2DL2 and the corresponding HLA-C ligand were initially recruited to the peripheral supramolecular activation cluster (pSMAC). Consequently, KIR2DL2 engagement did not inhibit the phosphorylation of early signaling proteins and T-cell–receptor (TCR)–mediated cytotoxicity or granule exocytosis. After 15-30 minutes, KIR2DL2 moved to the central supramolecular activation cluster (cSMAC), colocalizing with CD3. TCR synapses dissociated, and phosphorylated phospholipase C (PLC)–1, Vav1, and extracellular signal–regulated kinase 1/2 (ERK1/2) were reduced 90 minutes after stimulation. Gene array studies documented that the inhibition of late signaling events by KIR2DL2 affected transcriptional gene activation. We propose that KIRs on memory T cells operate to uncouple effector functions by modifying the transcriptional profile while leaving granule exocytosis unabated. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. van Bergen, E. M. C. Kooy-Winkelaar, H. van Dongen, F. A. van Gaalen, A. Thompson, T. W. J. Huizinga, M. C. W. Feltkamp, R. E. M. Toes, and F. Koning Functional Killer Ig-Like Receptors on Human Memory CD4+ T Cells Specific for Cytomegalovirus J. Immunol., April 1, 2009; 182(7): 4175 - 4182. [Abstract] [Full Text] [PDF] L. T. van der Veken, M. Diez Campelo, M. A. W. G. van der Hoorn, R. S. Hagedoorn, H. M. E. van Egmond, J. van Bergen, R. Willemze, J. H. F. Falkenburg, and M. H. M. Heemskerk Functional Analysis of Killer Ig-Like Receptor-Expressing Cytomegalovirus-Specific CD8+ T Cells J. Immunol., January 1, 2009; 182(1): 92 - 101. [Abstract] [Full Text] [PDF] B. R. Long, L. C. Ndhlovu, J. R. Oksenberg, L. L. Lanier, F. M. Hecht, D. F. Nixon, and J. D. Barbour Conferral of Enhanced Natural Killer Cell Function by KIR3DS1 in Early Human Immunodeficiency Virus Type 1 Infection J. Virol., May 15, 2008; 82(10): 4785 - 4792. [Abstract] [Full Text] [PDF] A. van Stijn, A. T. Rowshani, S. L. Yong, F. Baas, E. Roosnek, I. J. M. ten Berge, and R. A. W. van Lier Human Cytomegalovirus Infection Induces a Rapid and Sustained Change in the Expression of NK Cell Receptors on CD8+ T Cells J. Immunol., April 1, 2008; 180(7): 4550 - 4560. [Abstract] [Full Text] [PDF] J. Endt, F. E. McCann, C. R. Almeida, D. Urlaub, R. Leung, D. Pende, D. M. Davis, and C. Watzl Inhibitory Receptor Signals Suppress Ligation-Induced Recruitment of NKG2D to GM1-Rich Membrane Domains at the Human NK Cell Immune Synapse J. Immunol., May 1, 2007; 178(9): 5606 - 5611. [Abstract] [Full Text] [PDF]

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