LY-49 MULTIGENE FAMILY EXPRESSED BY IL-2-ACTIVATED NK CELLS

The susceptibility of a target cell to killing by NK cells is inversel y 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 w ith polymorphic regions of certain MHC class I molecules on target cel ls, 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 un derstanding 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 inhibitor y receptor function. We now report the isolation of cDNAs, encoding po lypeptides related to Ly-49, from a CD3(-), IL-2-activated NK cell lib rary. Full length PCR products were also cloned and sequenced, confirm ing 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 superfa mily homology and 66 to 79% amino acid identity with Ly-49A. In contra st to previous reports, these cDNAs cannot be allelic variants because they were all isolated from C57BL/6-derived cells. On the basis of nu cleotide homology, the cDNAs could be segregated into five groups; one with Ly-49 itself (now termed Ly-49A) and four others containing dist inct sequences. One of the new groups comprised three cDNAs that share d identical sequences, but differed from one another by deletions or i nsertions of short DNA segments in the predicted extracellular region of the polypeptides. Thus, IL-2-activated NK cells express mRNAs for m ultiple, Ly-49-related molecules.