Structure of human histocompatibility leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor

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, c omplexed with a nonameric consensus peptide (QYDDAVYKL). Relative to HLA-A2 , the peptide binding groove is widened around the COOH terminus of the alp ha 1 helix, which contains residues that determine the specificity of HLA-C w4 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 o f HLA-Cw4 has electrostatic complementarity to the surface of the NK cell i nhibitory receptor KIR2D.