NK cells do not express recombination-dependent antigen-specific receptors and are traditionally defined as cells of the innate immune response. The activation of NK cells was believed to be controlled by the net balance of signals from a multitude of activating and inhibitory receptors irrespectively of antigen specificity. However, murine antigenspecific memory NK cells in liver have been described to mediate hapten or viral specific recall response and are capable of infiltrating to the site of infection. The mechanisms by which NK cells recognize target cells in an antigen-specific manner are largely unclear. Using a novel multiplex killing assay, we screened the NK cell (human) cytotoxic activity of 35 different donors against different virus peptide pools loaded autologous B cells. We have found that human NK cells from some CMV and EBV positive donors can recognize peptide loaded autologous B cells as targets and perform antigen-specific cytotoxic killing. This may provide evidence that NK cells are able to scan the peptide repertoire on the target cell surface and virus-derived peptides may influence the NK cell activation-inhibition balance.