Murine NKG2D ligands: "double, double toil and trouble".
Unlike T and B cells, NK cells lack variable, clonotypic receptors that recognize foreign antigens. Instead, NK cells depend on conserved receptors such as NKG2D. NKG2D recognizes a variety of inducible self-proteins that belong to the non-classical MHC class I family. They include ULBP (1-3), MIC (A & B) in human and H60 (a, b & c), Rae-1 (alpha-epsilon) and Mult1 in mice. These self-proteins are expressed due to pathological stimuli, share limited amino acid homology and form the molecular basis for NKG2D-mediated activation. Recent studies have vastly improved our understanding of NKG2D receptor-mediated activation, signaling and function. However, a detailed knowledge on the immunobiology of its ligands is lacking. How many is too many? Is NKG2D the only receptor for these ligands? Where are these ligands expressed? What are the molecular mechanisms that regulate their expression? Do normal cells express these ligands? Does the communication between NKG2D receptor and its ligands travel through a two way road? If so, what do the 'target' cells get in turn, only death? How efficient are these ligands as molecular targets for NK cell-mediated tumor immunotherapy?
Samarakoon
Asanga
A
Laboratory of Molecular Immunology, Blood Research Institute, Division of Neoplastic Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
Chu
Haiyan
H
Malarkannan
Subramaniam
S
D000595:Amino Acid Sequence; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010802:Phylogeny; D011487:Protein Conformation; D015398:Signal Transduction / Q000276:immunology
D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K