Nk Cell Receptors

Abstract

NK cells are regulated by opposing signals from receptors that activate and inhibit effector function. While positive stimulation may be initiated by an array of costimulatory receptors, specificity is provided by inhibitory signals transduced by receptors for MHC class I. Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules. A common pathway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these otherwise structurally diverse receptors. Upon ligand binding and activation, the inhibitory NK cell receptors become tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 and possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxicity and cytokine expression. Recent studies suggest these inhibitory NK cell receptors are members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS).

Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

“…Progress is mainly consequent to the discovery of a series of receptors, expressed at the NK cell surface, regulating NK cell functions. Some of these receptors inhibit NK cells by monitoring the expression of MHC class I molecules on normal cells 1 2 3. Other receptors are responsible for NK cell activation 4.…”

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

“…Outcomes of NK cell‐target cell interactions are regulated by a fine integrative balance between inhibitory and activating receptors expressed on NK cells and their ligands on target cells 37. In addition, several studies have indicated that a majority of CRC show diminished MHC class I expression, making them particularly vulnerable to NK cell‐mediated killing and these patients show survival benefit 38, 39.…”

Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity

“…NKG2D recognizes nonclassical MHC-I molecules, such as MICA/MICB and UL16-binding proteins (ULBPs). The activating KIR recognizes classical MHC-I molecules, whereas the identification of the ligands for NCR has only recently begun [23,25]. Binding of TRAIL to TRAIL-R1 or TRAIL-R2 leads to receptor trimerisation and formation of the deathinducing signalling complex (DISC).…”