Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex

Nat Immunol. 2001 May;2(5):452-60. doi: 10.1038/87766.


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 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dimerization
  • Evolution, Molecular
  • HLA-C Antigens / chemistry*
  • Humans
  • Hydrogen Bonding
  • Killer Cells, Natural / immunology*
  • Lysine / chemistry
  • Models, Molecular
  • Protein Conformation
  • Receptors, Immunologic / chemistry*
  • Receptors, KIR2DL1
  • Species Specificity
  • Surface Properties


  • HLA-C Antigens
  • HLA-C*04 antigen
  • Receptors, Immunologic
  • Receptors, KIR2DL1
  • Lysine