Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses.
After accumulation of target cell human leukocyte antigen (HLA)-C at inhibitory natural killer (NK) cell immune synapses, some HLA-C transfers from target cells to NK cell plasma membranes and cytoplasm. This unexpected intercellular transfer of HLA-C is dependent on NK receptor recognition, since HLA-Cw6 or -Cw4 but not -Cw3 transfer to an NK transfectant expressing killer Ig-like receptor (KIR)2DL1. Strikingly, live-cell time-lapse laser scanning confocal microscopy shows vesicles containing target cell green fluorescent protein-tagged HLA-C migrating away from immune synapses into NK cells. Unlike clustering of HLA-C at the immune synapse, intercellular transfer of HLA-C is dependent on NK cell ATP, but not target cell ATP. However, the intercellular transfer of HLA-C is not dependent on active polymerization of the actin cytoskeleton. In addition, different arrangements of HLA-C are seen at inhibitory NK immune synapses, and these alter as NK synapses mature, but in a fashion distinct from that seen upon T cell activation.
Carlin
L M
LM
Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College of Science, Technology, and Medicine, South Kensington, London SW7 2AZ, United Kingdom.
Eleme
K
K
McCann
F E
FE
Davis
D M
DM
D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D015236:HLA-C Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D054342:Receptors, KIR2DL1; D013569:Synapses / Q000378:metabolism*
D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D000255:Adenosine Triphosphate