The YE1/32.8.5 antibody reacts with Ly-49A, a member of the C-type lectin family of proteins. Ly-49A is a type II transmembrane protein expressed as a 44 kDa disulfide-linked homodimer on the surface of subsets of natural killer (NK) cells, NK-T cells, and T cells by some mammalian species, but not humans. It functions to inhibit NK cell activation by binding to certain haplotypes of MHC class I molecules on target cells, specifically H-2Dd and H2Dk, which results in phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic domain and the recruitment of tyrosine phosphatases, such as SHP-1 and SHP-2. While many anti-Ly-49A antibodies are strain-specific, the YE1/32.8.5 antibody reacts with NK cells from all strains of mice tested. This antibody inhibits the binding of Ly-49A to its ligands and reverses the inhibition of NK cytotoxicity mediated by specific MHC class I molecules on target cells. It very weakly cross-reacts with Ly-49D, but the levels of cross-reactivity are deemed too low to affect flow cytometric analysis of NK cells for functional studies of Ly-49A.