Structural basis of MHC class I recognition by natural killer cell receptors

Immunol Rev. 2001 Jun:181:52-65. doi: 10.1034/j.1600-065x.2001.1810104.x.

Abstract

Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures have been reported for the complex between Ly49A and H-2Dd, and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Ly*
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • H-2 Antigens / chemistry
  • H-2 Antigens / metabolism
  • HLA-C Antigens / chemistry
  • HLA-C Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Histocompatibility Antigens Class I* / chemistry
  • Histocompatibility Antigens Class I* / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type
  • Leukocyte Immunoglobulin-like Receptor B1
  • Ligands
  • Macromolecular Substances
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • NK Cell Lectin-Like Receptor Subfamily A
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, NK Cell Lectin-Like
  • Sequence Homology, Amino Acid

Substances

  • Antigens, CD
  • Antigens, Ly
  • Carrier Proteins
  • H-2 Antigens
  • HLA-C Antigens
  • HLA-C*03 antigen
  • Histocompatibility Antigen H-2D
  • Histocompatibility Antigens Class I
  • KIR2DL2 protein, human
  • Klra1 protein, mouse
  • LILRB1 protein, human
  • Lectins, C-Type
  • Leukocyte Immunoglobulin-like Receptor B1
  • Ligands
  • Macromolecular Substances
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily A
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, NK Cell Lectin-Like