Crystal structure of the human natural killer cell inhibitory receptor KIR2DLI-HLA-Cw4 complex

Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells.We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DLI (KIR2DLI) bound to its class I MHC ligand, HLA-Cw4,The KIR2DLI-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DLI that hosts the Lys(80) residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DLI-HLA-Cw4 and in a previously reported KIR2DLI-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DLI-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee hips with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by hips.