Expression of natural killer receptor alleles at different Ly49 loci occurs independently and is regulated by major histocompatibility complex class I molecules

Ly49 receptor genes are expressed by subsets of natural killer (NK) cells i n an overlapping fashion, accounting for the capacity of NK subsets to atta ck host cells that have selectively downregulated self-major histocompatibi lity complex (MHC) class I molecules. It was shown previously that most NK cells express only one or the other allele of a given Ly49 gene, while a sm aller population expresses both alleles. However, the methods used to detec t monoallelic and biallelic cells were nonquantitative. Here, new allele-sp ecific antibodies were used to provide the first quantitative examination o f biallelic and monoallelic expression of Ly49A and Ly49G2. The results dem onstrate conclusively that most Ly49A(+) and Ly49G2(+) NK cells express the corresponding gene in a monoallelic fashion, with a smaller subset express ing both alleles. Unexpectedly, biallelic Ly49(+) NK cells were more numero us than predicted by completely independent allelic expression, suggesting some heterogeneity among NK progenitors in the potential to express a given Ly49 gene. The data also show that cells expressing one allele of Ly49G2 m ay express Ly49A from the same or opposite chromosome with equal likelihood , indicating that the expressed allele is chosen independently for differen t Ly49 genes. Finally, the data demonstrate that biallelic expression of Ly 49A or Ly49G2 occurs least frequently in mice that express ligands for thes e receptors (H-2(d) mice), and most frequently in class I-deficient mice. T hus, biallelic expression of Ly49 genes is regulated by interactions of NK cell progenitors with MHC class I molecules.