Ly49Q is a member of the Ly49 family that is expressed on Gr-1+ cells but not on NK and NKT cells. Ly49Q appears to be involved in regulating cytoskeletal architectures through ITIM-mediated signaling. We provide evidence that dendritic cells (DCs) of certain maturational states expressed Ly49Q, and that IFN-alpha plays an important role in its regulation. Freshly prepared murine plasmacytoid pre-DCs as well as Flt3L-induced plasmacytoid pre-DCs expressed Ly49Q, whereas freshly prepared myeloid DCs did not. However, GM-CSF-induced myeloid DCs showed low levels of Ly49Q expression, and this was significantly enhanced by IFN-alpha. In contrast, other cytokines and ligands for TLRs such as TNF-alpha, IL-6, LPS, and CpG-ODN had little or no effect on Ly49Q expression. Plasmacytoid pre-DCs in all mouse strains examined expressed Ly49Q. Constitutive expression of Ly49Q on myeloid DCs was observed in three restricted mouse strains including 129, NZB, and NZW. As can be seen in other Ly49 family members, Ly49Q expression was affected by MHC class I expression. At the same time, Ly49Q possessed polymorphisms, including at least three alleles. The polymorphic residues lay within the stalk and carbohydrate recognition domain, and two of them, in loop 3 and loop 6 of the carbohydrate recognition domain, are located in the region implicated in the interaction of Ly49A with H-2D(d). Therefore, depending on IFN-alpha, our results imply that Ly49Q serves a role for the biological functions of certain DC subsets through recognition of MHC class I or related molecules.