Acquisition of external major histocompatibility complex class I moleculesby natural killer cells expressing inhibitory Ly49 receptors

Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. We report th at during interactions with cells in the environment, NK cells acquired MHC class I ligands from surrounding cells in a Ly49-specific fashion and disp layed them at the cell surface. Ligand acquisition sometimes reached 20% of the MHC class I expression on surrounding cells, involved transfer of the entire MHC class I protein to the NK cell, and was independent of whether o r not the NK cell expressed the MHC class I ligand itself. We also present indirect evidence for spontaneous MHC class I acquisition in vivo, as well as describe an in vitro coculture system with transfected cells in which th e same phenomenon occurred. Functional studies in the latter model showed t hat uptake of H-2D(d) by Ly49A(+) NK cells was accompanied by a partial ina ctivation of cytotoxic activity in the NK cell, as tested against H-2D(d)-n egative target cells. In addition, ligand acquisition did not abrogate the ability of Ly49A(+) NK cells to receive inhibitory signals from external H- 2D(d) molecules. This study is the first to describe ligand acquisition by NK cells, which parallels recently described phenomena in T and B cells.