Natural killer cell recognition of HLA class I molecules

Rev Immunogenet. 2000;2(3):433-48.

Abstract

Human NK cells express multiple receptors that interact with HLA class I molecules. These receptors belong to one of two major protein superfamilies, the immunoglobulin superfamily or the C type lectin superfamily. The killer cell immunoglobulin-like receptor (KIR) family predominantly recognise classical HLA class I molecules and different family members interact with discrete HLA class I allotypes. The solution of the crystal structure of KIR2DL2 in complex with its ligand, HLA-Cw3 has provided the molecular details of a KIR/class I interaction. The interaction site spans both the alpha1 and alpha2 helices of class I and the KIR makes direct contact with peptide residues 7 and 8. The allotype specificity of KIR2DL2 for HLA-Cw3 is the result of a single hydrogen bond from Lys44 of the KIR to Asn80 of HLA-C as all other HLA-C residues that contact KIR are conserved. The lectin-like CD94/NKG2 receptors specifically interact with the non-classical class I molecule, HLA-E. Cell surface expression of HLA-E is dependent on the expression of other class I molecules as they are the major source of HLA-E binding peptides in normal cells. Consequently recognition of HLA-E by the CD94/NKG2 receptors allows NK cells to indirectly monitor the expression of a broad array of class I molecules. While the molecular interactions underlying ligand recognition by both KIR and CD94/NKG2 receptors are likely to be distinct, recognition of class I by both families of receptors appears peptide dependent. This suggest that cells that lack class I and also those that are impaired in their ability to load class I molecules with peptide will become targets for NK-mediated destruction.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / immunology
  • Binding Sites
  • Cytotoxicity, Immunologic
  • Dimerization
  • HLA Antigens / chemistry
  • HLA Antigens / immunology
  • HLA-C Antigens / chemistry
  • HLA-C Antigens / immunology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Hydrogen Bonding
  • Lectins, C-Type*
  • Leukocyte Immunoglobulin-like Receptor B1
  • Macromolecular Substances
  • Membrane Glycoproteins / immunology
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, Natural Killer Cell
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Zinc / physiology

Substances

  • Antigens, CD
  • HLA Antigens
  • HLA-C Antigens
  • HLA-C*03 antigen
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • KIR2DL2 protein, human
  • KLRC1 protein, human
  • KLRD1 protein, human
  • LILRB1 protein, human
  • Lectins, C-Type
  • Leukocyte Immunoglobulin-like Receptor B1
  • Macromolecular Substances
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptide Fragments
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, Natural Killer Cell
  • Zinc