CD160 activating NK cell receptor is a glycosylphosphatidylinositol-anchored molecule. Upon specific engagement by its HLA class I physiological ligand, CD160 NK cell receptor triggers cytotoxicity and release of different cytokines, including IL-6. How CD160 intracellular signaling is mediated following its specific ligation is unknown. One key element of this signaling may be through the co-activation of other receptors associated to CD160. Using confocal microscopy and freshly isolated human peripheral blood NK cells, we observed a co-polarization of CD160 and CD2 after their respective specific engagement. These results demonstrate that CD160 activating NK cell receptor, upon its specific engagement, physically associates to the CD2 co-activating receptor present in the lipid raft that might play a role as signaling molecule.