EXPRESSION OF DIFFERENT MEMBERS OF THE LY-49 GENE FAMILY DEFINES DISTINCT NATURAL-KILLER-CELL SUBSETS AND CELL-ADHESION PROPERTIES

The murine Ly-49 antigen belongs to a family of type II transmembrane molecules containing lectin-like domains. The original member of this family, Ly-49A, has been demonstrated to be expressed by a subpopulati on of natural killer (NK) cells, bind certain class I major histocompa tibility complexes (MHC), and act as a negative regulator of lytic act ivity. The expression patterns and functional activities of the other Ly-49s, however, is unknown. We extended the study of this family by i solating cDNAs encoding two new Ly-49 molecules. The reactivity of the se and previously identified Ly-49 molecules with NK antibodies was te sted in a COS cell expression system. YE1/32 and YE1/48 bound Ly-49A s pecifically, and 5E6 reacted only with Ly-49C. Three-color flow cytome tric analysis demonstrated that Ly-49A and Ly-49C expression defines c omplex, but distinct subsets within NK1.1(+) cells. Some NK1.1 CD3(+) as well as NK1.1-CD3(-) cells expressing Ly-49A or C were also detecte d. Analysis of MHC congenic strains of mice demonstrated that YE1/32() and YE1/48(+) NK cells are not deleted, as has been shown with the L y-49A mAb A1. Furthermore, COS cells transfected with Ly-49A bound H-2 (d) and H-2(k) cell lines, whereas Ly-49C transfectants bound H-2(d), H-2(k), H-2(b), and H-2(s). The antibodies 5E6 and 34-1-2S (anti-class I MHC) inhibited the binding of Ly-49C to an H-2(s) cell line. These results imply that the NK cell antigens Ly-49A and C bind to different repertoires of class I MHC molecules.