The human natural killer cell immune synapse.
Inhibitory killer Ig-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 cells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distributed into rings around central patches of intercellular adhesion molecule-1/lymphocyte 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. Clustering required a divalent metal cation, explaining how metal chelators inhibit KIR function. Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine and cytochalsins B and D. Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.
Davis
D M
DM
Department of Molecular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02143, USA.
Chiu
I
I
Fassett
M
M
Cohen
G B
GB
Mandelboim
O
O
Strominger
J L
JL
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002413:Cations, Divalent; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D049452:Green Fluorescent Proteins; D015236:HLA-C Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007152:Immunologic Capping; D007694:Killer Cells, Natural / Q000276:immunology*; D008164:Luminescent Proteins / Q000235:genetics; D009068:Movement; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D002413:Cations, Divalent; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D008164:Luminescent Proteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate