Background: Natural killer (NK) cells use inhibitory Ly49 receptors to differentiate self from foreign cells based on interactions with major histocompatibility (MHC) class I molecules. Inhibitory receptors may recognize multiple MHC class I molecules. Studies to define ligands for the Ly49 receptors are complicated by the fact that receptors are expressed in overlapping subsets on NK cells. Binding studies can predict which MHC class I molecules are ligands for Ly49 receptors, but functional tests are required to substantiate results from binding studies.
Methods: We developed Ly49 receptor transgenic mice and studied the function of Ly49I(B6) in FVB.Ly49I(B6) transgenic mice using bone marrow transplantation assays to determine additional functional ligands for Ly49I(B6). We have also used fluorescence-activated cell sorting to isolate specific populations of B6 NK cells bearing Ly49I for use as effectors in chromium-release assays against a panel of Concanavalin A blast targets.
Results: Bone marrow transplantation studies indicate that H2-K(b), H2(s), and H2(v) serve as functional ligands for Ly49I(B6). In vitro cytotoxicity assays indicate that Ly49I recognizes H2(q), but not H2(d) or H2(k), target cells to inhibit NK killing.
Conclusions: These data add support to previous binding studies by showing functional interactions between the B6-strain Ly49I and H2-K(b), H2(s), H2(v), and H2(q) class I antigens.