Ly-49 multigene family expressed by IL-2-activated NK cells

The susceptibility of a target cell to killing by NK cells is inversely correlated with target cell expression of MHC class I molecules. We have recently demonstrated that a murine NK cell surface molecule, Ly-49, is a primary determinant of IL-2-activated NK cell specificity by apparently acting as an inhibitory receptor. Ly-49 seems to interact with polymorphic regions of certain MHC class I molecules on target cells, yet is expressed only by a subset (15 to 20%) of NK cells. If the interaction between Ly-49 and MHC class I represents a paradigm for understanding IL-2-activated NK cell specificity and putative inhibitory IL-2-activated NK cell receptors, these effector cells should express other molecules, perhaps related to Ly-49, that provide the inhibitory receptor function. We now report the isolation of cDNAs, encoding polypeptides related to Ly-49, from a CD3-, IL-2-activated NK cell library. Full length PCR products were also cloned and sequenced, confirming expression in IL-2-activated NK cells. These cDNAs were homologous to the Ly-49 cDNA and seem to be derived from distinct genes. The new cDNAs encode type II integral membrane proteins having lectin superfamily homology and 66 to 79% amino acid identity with Ly-49A. In contrast to previous reports, these cDNAs cannot be allelic variants because they were all isolated from C57BL/6-derived cells. On the basis of nucleotide homology, the cDNAs could be segregated into five groups; one with Ly-49 itself (now termed Ly-49A) and four others containing distinct sequences. One of the new groups comprised three cDNAs that shared identical sequences, but differed from one another by deletions or insertions of short DNA segments in the predicted extracellular region of the polypeptides. Thus, IL-2-activated NK cells express mRNAs for multiple, Ly-49-related molecules.