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Intercellular Transfer and Supramolecular Organization of Human Leukocyte Antigen C at Inhibitory Natural Killer Cell Immune Synapses

Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College of Science, Technology, and Medicine, London SW7 2AZ, United Kingdom

Address correspondence to Daniel M. Davis, Dept. of Biological Sciences Sir Alexander Fleming Bldg, Imperial College of Science, Technology, and Medicine, South Kensington, London SW7 2AZ, UK. Phone: 44-207-594-5420; Fax: 44-207-584-2056; E-mail: d.davis{at}ic.ac.uk

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.

Key Words: MHC class I • KIR • green fluorescent protein • immunosurveillance • laser scanning confocal microscopy

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