Ly-49A is a 44 kD member of the C-type lectin/Ly-49 family proteins. It is a type-II transmembrane, disulfide-linked homodimer with C-type lectin extracellular domains. Ly-49A is present on a subset of NK and NK-T cells. Ly-49A, like other members of this family, inhibits NK cell activation through the recognition and interaction of certain MHC class I haplotypes on potential target cells. The Ly-49A receptor recognizes H-2Dd and H-2Dk, triggering phosphorylation of the ITIM motif in the cytoplasmic domain and recruitment of SHP-1 and SHP-2. The YE1/48.10.6 antibody reacts with NK cells from all mouse strains tested and reverses the inhibition of NK cytotoxicity.