The human natural killer cell immune synapse

Inhibitory killer lg-like receptors (KIR) at the surface of natural killer (NK) cells induced clustering of HLA-C at the contacting surface of target cells. In this manner, inhibitory immune synapses were formed as human NK c ells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distribut ed into rings around central patches of intercellular adhesion molecule-1/l ymphocyte function-associated antigen-1, the opposite orientation to mature murine T cell-activating synapses. This organization of protein was stable for at least 20 min. Cells could support multiple synapses simultaneously, and clusters of HLA-C moved as NK cells crawled over target cells, Cluster ing required a divalent metal cation, explaining how metal chelators inhibi t KIR function, Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine an d cytochalsins B and D, Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.