HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McCann, F. E. Articles by Davis, D. M. Search for Related Content PubMed PubMed Citation Articles by McCann, F. E. Articles by Davis, D. M.

The Size of the Synaptic Cleft and Distinct Distributions of Filamentous Actin, Ezrin, CD43, and CD45 at Activating and Inhibitory Human NK Cell Immune Synapses ^1,2

Fiona E. McCann^*, Bruno Vanherberghen^*, Konstantina Eleme^*, Leo M. Carlin^*, Ray J. Newsam, David Goulding and Daniel M. Davis^3,*

^* Department of Biological Sciences and Center for Molecular Microbiology and Infection, Imperial College, London, United Kingdom; and Research School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom

In this study, we report the organization of cytoskeletal and large transmembrane proteins at the inhibitory and activating NK cell immunological or immune synapse (IS). Filamentous actin accumulates at the activating, but not the inhibitory, NK cell IS. However, surprisingly, ezrin and the associated protein CD43 are excluded from the inhibitory, but not the activating, NK cell IS. This distribution of ezrin and CD43 at the inhibitory NK cell IS is similar to that previously seen at the activating T cell IS. CD45 is also excluded from the inhibitory, but not activating, NK cell IS. In addition, electron microscopy reveals wide and narrow domains across the synaptic cleft. Target cell HLA-C, located by immunogold labeling, clusters where the synaptic cleft spans the size of HLA-C bound to the inhibitory killer Ig-like receptor. These data are consistent with assembly of the NK cell IS involving a combination of cytoskeletal-driven mechanisms and thermodynamics favoring the organization of receptor/ligand pairs according to the size of their extracellular domains.

This article has been cited by other articles:

				V. L. Hegde, N. P. Singh, P. S. Nagarkatti, and M. Nagarkatti CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation J. Leukoc. Biol., July 1, 2008; 84(1): 134 - 142. [Abstract] [Full Text] [PDF]

				A. Pierres, A.-M. Benoliel, D. Touchard, and P. Bongrand How Cells Tiptoe on Adhesive Surfaces before Sticking Biophys. J., May 15, 2008; 94(10): 4114 - 4122. [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]

				S. Nedvetzki, S. Sowinski, R. A. Eagle, J. Harris, F. Vely, D. Pende, J. Trowsdale, E. Vivier, S. Gordon, and D. M. Davis Reciprocal regulation of human natural killer cells and macrophages associated with distinct immune synapses Blood, May 1, 2007; 109(9): 3776 - 3785. [Abstract] [Full Text] [PDF]

				F. E. McCann, P. Eissmann, B. Onfelt, R. Leung, and D. M. Davis The Activating NKG2D Ligand MHC Class I-Related Chain A Transfers from Target Cells to NK Cells in a Manner That Allows Functional Consequences J. Immunol., March 15, 2007; 178(6): 3418 - 3426. [Abstract] [Full Text] [PDF]

				E. N. M. Nolte-'t Hoen, C. R. Almeida, N. R. Cohen, S. Nedvetzki, H. Yarwood, and D. M. Davis Increased surveillance of cells in mitosis by human NK cells suggests a novel strategy for limiting tumor growth and viral replication Blood, January 15, 2007; 109(2): 670 - 673. [Abstract] [Full Text] [PDF]

				C. R. Almeida and D. M. Davis Segregation of HLA-C from ICAM-1 at NK Cell Immune Synapses Is Controlled by Its Cell Surface Density J. Immunol., November 15, 2006; 177(10): 6904 - 6910. [Abstract] [Full Text] [PDF]

				M. Masilamani, C. Nguyen, J. Kabat, F. Borrego, and J. E. Coligan CD94/NKG2A Inhibits NK Cell Activation by Disrupting the Actin Network at the Immunological Synapse J. Immunol., September 15, 2006; 177(6): 3590 - 3596. [Abstract] [Full Text] [PDF]

				D. B. Graham, M. Cella, E. Giurisato, K. Fujikawa, A. V. Miletic, T. Kloeppel, K. Brim, T. Takai, A. S. Shaw, M. Colonna, et al. Vav1 Controls DAP10-Mediated Natural Cytotoxicity by Regulating Actin and Microtubule Dynamics J. Immunol., August 15, 2006; 177(4): 2349 - 2355. [Abstract] [Full Text] [PDF]

				D. S. Korbel, K. C. Newman, C. R. Almeida, D. M. Davis, and E. M. Riley Heterogeneous Human NK Cell Responses to Plasmodium falciparum-Infected Erythrocytes J. Immunol., December 1, 2005; 175(11): 7466 - 7473. [Abstract] [Full Text] [PDF]

				H. D. Kopcow, D. S. J. Allan, X. Chen, B. Rybalov, M. M. Andzelm, B. Ge, and J. L. Strominger Human decidual NK cells form immature activating synapses and are not cytotoxic PNAS, October 25, 2005; 102(43): 15563 - 15568. [Abstract] [Full Text] [PDF]

				A. Jansson, E. Barnes, P. Klenerman, M. Harlen, P. Sorensen, S. J. Davis, and P. Nilsson A Theoretical Framework for Quantitative Analysis of the Molecular Basis of Costimulation J. Immunol., August 1, 2005; 175(3): 1575 - 1585. [Abstract] [Full Text] [PDF]

				E.-K. Jo, H. Wang, and C. E. Rudd An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R J. Exp. Med., June 6, 2005; 201(11): 1733 - 1739. [Abstract] [Full Text] [PDF]

				M. Poupot, F. Pont, and J.-J. Fournie Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human {gamma}{delta} T Cells to Anaplastic Large Cell Lymphoma J. Immunol., February 1, 2005; 174(3): 1717 - 1722. [Abstract] [Full Text] [PDF]

				B. Vanherberghen, K. Andersson, L. M. Carlin, E. N. M. Nolte-`t Hoen, G. S. Williams, P. Hoglund, and D. M. Davis Human and murine inhibitory natural killer cell receptors transfer from natural killer cells to target cells PNAS, November 30, 2004; 101(48): 16873 - 16878. [Abstract] [Full Text] [PDF]

				L. J. Standeven, L. M. Carlin, P. Borszcz, D. M. Davis, and D. N. Burshtyn The Actin Cytoskeleton Controls the Efficiency of Killer Ig-Like Receptor Accumulation at Inhibitory NK Cell Immune Synapses J. Immunol., November 1, 2004; 173(9): 5617 - 5625. [Abstract] [Full Text] [PDF]

				H. Wang, F. E. McCann, J. D. Gordan, X. Wu, M. Raab, T. H. Malik, D. M. Davis, and C. E. Rudd ADAP-SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell-APC Conjugation J. Exp. Med., October 18, 2004; 200(8): 1063 - 1074. [Abstract] [Full Text] [PDF]

				P. Roda-Navarro, M. Mittelbrunn, M. Ortega, D. Howie, C. Terhorst, F. Sanchez-Madrid, and E. Fernandez-Ruiz Dynamic Redistribution of the Activating 2B4/SAP Complex at the Cytotoxic NK Cell Immune Synapse J. Immunol., September 15, 2004; 173(6): 3640 - 3646. [Abstract] [Full Text] [PDF]

				K. Eleme, S. B. Taner, B. Onfelt, L. M. Collinson, F. E. McCann, N. J. Chalupny, D. Cosman, C. Hopkins, A. I. Magee, and D. M. Davis Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D J. Exp. Med., April 5, 2004; 199(7): 1005 - 1010. [Abstract] [Full Text] [PDF]

				Y. Kaizuka and J. T. Groves Structure and Dynamics of Supported Intermembrane Junctions Biophys. J., February 1, 2004; 86(2): 905 - 912. [Abstract] [Full Text] [PDF]