Abstract
The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). Relative to HLA-A2, the peptide binding groove is widened around the COOH terminus of the alpha 1 helix, which contains residues that determine the specificity of HLA-Cw4 for the inhibitory NK receptor, KIR2D. The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues. The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft. The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D.