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 inhibi tory natural killer (NK) cell immune synapses, some HLA-C transfers from ta rget cells to NK cell plasma membranes and cytoplasm. This unexpected inter cellular transfer of HLA-C is dependent on NK receptor recognition, since H LA-Cw6 or -Cw4 but not -Cw3 transfer to an NK transfectant expressing kille r Ig-like receptor (KIR)2DL1. Strikingly, live-cell time-lapse laser scanni ng confocal microscopy shows vesicles containing target cell green fluoresc ent protein-tagged HLA-C migrating away from immune synapses into NK cells. Unlike clustering of HLA-C at the immune synapse, intercellular transfer o f 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 matu re, but in a fashion distinct from that seen upon T cell activation.