Genetic investigation of MHC-independent missing-self recognition by natural killer cells

Natural killer (NK) cells are necessary for the destruction of infected and cancerous cells. NK cell function is regulated by two broad mechanisms: 1) MHC-related; 2) MHC-independent. Both categories involve receptors expressed on the surface of NK cells and turn off the NK cell when a healthy cell is encountered. The Nkrp1 mechanism is a newly described MHC-independent system involving recognition of the Clr family of ligands. Our goals are threefold: 1) to confirm that Nkrp1:Clr interactions regulate NK cell function in vivo, 2) to transfer Nkrp1 markers to commonly used mouse strains, and 3) to assess novel strain-dependent Nkrp1:Clr family interactions. This study will give insight into the mechanisms regulating MHC-independent NK cell function in mice. Extending our findings to homologous systems in humans may allow the manipulation of human NK cell function during anti-viral or anti-cancer responses.