NK cell licensing modulates NK cell conjugation to target cells via altered activation receptor function (P1063)

Abstract

Abstract MHC class I recognition by inhibitory receptors on natural killer (NK) cells promotes a state of increased NK cell responsiveness through a process known as licensing/education. In the absence of either MHC class I expression or inhibitory receptors, NK cells exhibit a decreased responsive state. Thus NK cell licensing is a critical aspect of NK cell biology. However, understanding how licensing modulates natural cytotoxicity is limited. Using pure populations of unlicensed human NK cells, we were able to evaluate the effect of licensing on several NK cell functions. Our findings reveal that NK cell licensing does not affect lytic granule polarization but significantly enhances NK cell conjugation to target cells. Furthermore, our data show that activation receptors in unlicensed NK cells fail to provide strong ‘inside-out’ signaling for the beta2 integrin LFA-1. NK cell adhesion to target cells is a crucial initial step in NK cell-mediated cytotoxicity. The reduced conjugation of unlicensed NK cells may contribute to their hyporesponsive state.