Allospecificities of B6D2F1 hybrid NK cell subsets defined by Ly-49A expression

More than 90% of IL-2-activated plastic-adherent murine splenocytes (A-LAK4 cells) are NK1.1+ NK cells and both H-2b/b homozygous C57BL/6- and H-2b/d heterozygous (C57BL/6 x DBA/2)F1 (B6D2F1)-derived populations of such cells contain an Ly-49A+ subset. In B6D2F1 A-LAK cells, as well as in freshly isolated spleen cells of the same mice, Ly-49A+ cells represent approximately 10% of NK1.1+ cells. However, the level of Ly-49A expression in B6D2F1 NK cells is lower than in C57BL/6 (B6). The cytolytic activity of B6- and B6D2F1-derived A-LAK cells against normal target cells is specific, and is in agreement with the known patterns of natural resistance in vivo against Hh-1-mismatched bone marrow allografts. H-2b lymphoma cells transfected with the Dd gene, but not the Ld gene, no longer express the Hh-1b phenotype that is recognized by B6D2F1 A-LAK cells, raising the possibility that this selective effect of the Dd gene on Hh-1b phenotype is related to the known inability of Ly-49A+ A-LAK cells to kill Dd-expressing tumor target cells. Depletion of Ly-49A+ A-LAK cells by Ab and complement reduces the lytic capacity of B6D2F1 A-LAK cells against normal B6 target cells of the Hh-1b phenotype to one-third of the original level. Conversely, positively selected Ly-49A+ A-LAK cells are enriched for the same activity. The results, therefore, favor the view that the Hh-1 phenotype of the target cells may be defined largely by the effector cell's recognition of class I Ags on the target cell surface.