Asymmetric ligand recognition by the activating natural killer cell receptor NKG2D, a symmetric homodimer

Mol Immunol. 2002 May;38(14):1029-37. doi: 10.1016/s0161-5890(02)00032-9.


Natural killer (NK) cells function through a diverse array of cell-surface natural killer receptors (NCRs). NCRs specific for classical and non-classical MHC class I proteins, expressed in complex patterns of inhibitory and activating isoforms on overlapping, but distinct, subsets of NK cells, play an important role in immunosurveillance against cells that have reduced MHC class I expression as a result of infection or transformation. Another NCR, NKG2D, is an activating NCR first identified on NK cells, but subsequently found on macrophages and a variety of T cell types. NKG2D ligands in rodents include the MHC class I-like proteins RAE-1 and H60 and, in humans, ULBPs and the cell stress-inducible proteins MICA and MICB. NKG2D-MIC and -RAE-1 recognition events have been implicated in anti-viral and -tumor immune responses. Crystallographic analyses of NKG2D-MICA and -RAE-1 complexes reveal an unusual mode of recognition that apparently tolerates a surprising degree of ligand plasticity while generating affinities that are among the strongest TCR- or NCR-ligand affinities, thus, far described.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Dimerization
  • Humans
  • Killer Cells, Natural / immunology*
  • Ligands
  • Lymphocyte Activation / immunology
  • Models, Molecular
  • NK Cell Lectin-Like Receptor Subfamily K
  • Protein Structure, Tertiary
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / immunology
  • Receptors, Natural Killer Cell
  • Solutions


  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Solutions