Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells.
Natural killer (NK) cells express receptors that are specific for MHC class I molecules. These receptors play a crucial role in regulating the lytic and cytokine expression capabilities of NK cells. In humans, three distinct families of genes have been defined that encode for receptors of HLA class I molecules. The first family identified consists of type I transmembrane molecules belonging to the immunoglobulin (Ig) superfamily and are called killer cell Ig-like receptors (KIR). A second group of receptors belonging to the Ig superfamily, named ILT (for immunoglobulin like transcripts), has more recently been described. ILTs are expressed mainly on B, T and myeloid cells, but some members of this group are also expressed on NK cells. They are also referred to as LIRs (for leukocyte Ig-like receptor) and MIRs (for macrophage Ig-like receptor). The ligands for the KIR and some of the ILT receptors include classical (class Ia) HLA class I molecules, as well as the nonclassical (class Ib) HLA-G molecule. The third family of HLA class I receptors are C-type lectin family members and are composed of heterodimers of CD94 covalently associated with a member of the NKG2 family of molecules. The ligand for most members is the nonclassical class I molecule HLA-E. NKG2D, a member of the NKG2 family, is expressed as a homodimer, along with the adaptor molecule DAP10. The ligands of NKG2D include the human class I like molecules MICA and MICB, and the recently described ULBPs. Each of these three families of receptors has individual members that can recognize identical or similar ligands yet signal for activation or inhibition of cellular functions. This dichotomy correlates with particular structural features present in the transmembrane and intracytoplasmic portions of these molecules. In this review we will discuss the molecular structure, specificity, cellular expression patterns, and function of these HLA class I receptors, as well as the chromosomal location and genetic organization.
Borrego
Francisco
F
Receptor Cell Biology Section, Laboratory of Allergic Diseases, NIAID, NIH, Twinbrook II, Room 205, 12441 Parklawn Dr., Rockville, MD 20852, USA.
Kabat
Juraj
J
Kim
Dae-Ki
DK
Lieto
Louis
L
Maasho
Kerima
K
Peña
José
J
Solana
Rafael
R
Coligan
John E
JE
D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; C527085:KLRK1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins