Class Ib major histocompatibility complex (MHC) is an extended family of molecules, which demonstrate tissue-specific expression and presentation of monomorphic antigens. These characteristics tend to imbue class Ib MHC with unique functions. H2-Q10 is potentially one such molecule that is overexpressed in the liver but its immunological function is not known. We have previously shown that H2-Q10 is a ligand for the natural killer cell receptor Ly49C and now, using H2-Q10-deficient mice, we demonstrate that H2-Q10 can also stabilize the expression of Qa-1b. In the absence of H2-Q10, the development and maturation of conventional hepatic natural killer cells is disrupted. We also provide evidence that H2-Q10 is a new high affinity ligand for CD8αα and controls the development of liver-resident CD8αα γδT cells. These data demonstrate that H2-Q10 has multiple roles in the development of immune subsets and identify an overlap of recognition within the class Ib MHC that is likely to be relevant to the regulation of immunity.