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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.

Original publication




Journal article


J Immunol

Publication Date





2862 - 2870


Actin Cytoskeleton, Actins, Antigens, CD, Cell Communication, Cell Line, Transformed, Clone Cells, Cytoskeletal Proteins, Cytotoxicity, Immunologic, HLA-C Antigens, Humans, Intercellular Junctions, Killer Cells, Natural, Leukocyte Common Antigens, Leukosialin, Lymphocyte Activation, Microscopy, Confocal, Microscopy, Immunoelectron, Phosphoproteins, Receptors, Immunologic, Receptors, KIR2DL1, Sialoglycoproteins, Tumor Cells, Cultured