The Human Natural Killer Cell Immune Synapse

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 26; pp. 15062 - 15067
• Main Authors: Davis, Daniel M., Chiu, Isaac, Fassett, Marlys, Cohen, George B., Mandelboim, Ofer, Strominger, Jack L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21-12-1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Actins - metabolism; Adenosine Triphosphate - metabolism; Biological Sciences; Blood; Cations, Divalent; Cell Adhesion; Cell lines; Cells; Cellular immunity; Cytochalasins; Cytoskeleton - metabolism; Cytotoxicity, Immunologic; Fluorescence; Green Fluorescent Proteins; histocompatibility antigen HLA; Histocompatibility Antigens Class I - immunology; HLA C antigens; HLA-C Antigens - genetics; HLA-C Antigens - metabolism; Humans; Immunologic Capping; Immunology; Killer Cells, Natural - immunology; Luminescent Proteins - genetics; Molecules; Movement; Natural killer cells; Proteins; Receptors; Receptors, Immunologic - metabolism; Receptors, KIR; Recombinant Fusion Proteins; Synapses; T lymphocytes; Tubulin - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.26.15062

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.