Ly-49W, an activating receptor of nonobese diabetic mice with close homology to the inhibitory receptor Ly-49G, recognizes H-2D(k) and H-2D(d)

The diversity and ligand specificity of activating Ly-49 receptors expresse d by murine NK cells are largely unknown. We cloned a new Ly-49-activating receptor, expressed by NK cells of the nonobese diabetic mouse strain, whic h we have designated Ly-49W, Ly-49W is highly related to the known inhibito ry receptor Ly-49G in its carbohydrate recognition domain, exhibiting 97.6% amino acid identity in this region. We demonstrate that the 4D11 and Cwy-3 Abs, thought to he Ly-49G specific, also recognize Ly-49W, Rat RNK-16 cell s transfected with Ly-49W mediated reverse Ab-dependent cellular cytotoxici ty of FcR-positive target cells, indicating that Ly-49W can activate NK-med iated lysis. We further show that Ly-49W is allo-MHC specific: Ly-49W trans fectants of RNK-16 only lysed Con A blasts expressing H-2(k) or H-2(d) hapl otypes, and Ab-blocking experiments indicated that H-2D(k) and D-d are liga nds for Ly-49W, Ly-49W is the first activating Ly-49 receptor demonstrated to recognize an H-2k class I product. Ly-49G and Ly-49W represent a new pai r of NK receptors with very similar ligand-binding domains, but opposite si gnaling functions.