Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules

The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K^b, D^b, D^d, or L^d) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K^b or D^d conveyed strong rejection of MHC class I-deficient cells, whereas the expression of Db or Ld resulted in weaker responses. The educating impact of weak ligands (D^b and L ^d) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K^b and D^d) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.