Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand

Nature. 2000 Jun 1;405(6786):537-43. doi: 10.1038/35014520.


Target cell lysis is regulated by natural killer (NK) cell receptors that recognize class I MHC molecules. Here we report the crystal structure of the human immunoglobulin-like NK cell receptor KIR2DL2 in complex with its class I ligand HLA-Cw3 and peptide. KIR binds in a nearly orthogonal orientation across the alpha1 and alpha2 helices of Cw3 and directly contacts positions 7 and 8 of the peptide. No significant conformational changes in KIR occur on complex formation. The receptor footprint on HLA overlaps with but is distinct from that of the T-cell receptor. Charge complementarity dominates the KIR/HLA interface and mutations that disrupt interface salt bridges substantially diminish binding. Most contacts in the complex are between KIR and conserved HLA-C residues, but a hydrogen bond between Lys 44 of KIR2DL2 and Asn 80 of Cw3 confers the allotype specificity. KIR contact requires position 8 of the peptide to be a residue smaller than valine. A second KIR/HLA interface produced an ordered receptor-ligand aggregation in the crystal which may resemble receptor clustering during immune synapse formation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Electrochemistry
  • Escherichia coli
  • HLA-C Antigens / chemistry*
  • HLA-C Antigens / immunology
  • Humans
  • Killer Cells, Natural / chemistry*
  • Killer Cells, Natural / immunology
  • Ligands
  • Major Histocompatibility Complex
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Receptor Aggregation
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / immunology
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology


  • HLA-C Antigens
  • HLA-C*03 antigen
  • KIR2DL2 protein, human
  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Recombinant Proteins

Associated data

  • PDB/1EFX