Learning how to discriminate between friends and enemies, a lesson from Natural Killer cells

NK Cells and Cancer

“…NK cells express surface receptors (NK cell receptors (NKR)) that can be classified as inhibitory and activatory (8,9). There are several inhibitory receptors with different molecular structures and specificities for different alleles of class I molecules, the two main groups being the killer Ig-like receptors (KIR) (8), which bind HLA-class I, and the heterodimeric receptors CD94-NKG2A/B, which recognize HLA-E (10).…”

“…There are several inhibitory receptors with different molecular structures and specificities for different alleles of class I molecules, the two main groups being the killer Ig-like receptors (KIR) (8), which bind HLA-class I, and the heterodimeric receptors CD94-NKG2A/B, which recognize HLA-E (10). The lack of even a single MHC-I allele, a frequent event in cancer cells, sensitizes them to NK cell cytotoxicity (8,9). For the same reason, NK cells kill host lymphohemopoietic cells that, expressing different HLA-I molecules, mismatch NK inhibitory receptors (KIR-mismatch) (11).…”

“…In the absence of inhibitory signals, however, NK cell cytotoxicity must be activated by a set of triggering receptors. Spontaneous cytotoxic activity is mainly triggered by NKG2D, leukocyte adhesion molecule DNAX accessory molecule 1 (DNAM-1) (CD226), and natural cytotoxicity receptors, whereas CD16, by binding the Fc portion of IgG, binds to opsonized cells mediating Ab-dependent cellular cytotoxicity (ADCC) (8,9,12). NKG2D and DNAM-1 recognize stress-induced ligands expressed by several tumor cell lines, such as MHC-I polypeptide-related sequence A, MHC-I polypeptide-related sequence B, and UL16-binding protein (NKG2D ligands), and poliovirus receptor (CD155) and Nectin-2 (CD112) (DNAM-1 ligands) (13)(14)(15).…”

“…NKG2D and DNAM-1 recognize stress-induced ligands expressed by several tumor cell lines, such as MHC-I polypeptide-related sequence A, MHC-I polypeptide-related sequence B, and UL16-binding protein (NKG2D ligands), and poliovirus receptor (CD155) and Nectin-2 (CD112) (DNAM-1 ligands) (13)(14)(15). Natural cytotoxicity receptors include now three molecules specific for unknown host ligands: NKp46, NKp30, and NKp44 (8,9), which mediate cell lysis of many cancer cells. Additional surface molecules have been implicated in NK cell activation and tumor cell lysis; these include 2B4, NTB-A, NKp80 coreceptors, CD18/CD11 (␤ 2 integrins), CD2 adhesion molecules, and TLR (8,9,12,16,17).…”

“…Natural cytotoxicity receptors include now three molecules specific for unknown host ligands: NKp46, NKp30, and NKp44 (8,9), which mediate cell lysis of many cancer cells. Additional surface molecules have been implicated in NK cell activation and tumor cell lysis; these include 2B4, NTB-A, NKp80 coreceptors, CD18/CD11 (␤ 2 integrins), CD2 adhesion molecules, and TLR (8,9,12,16,17). In particular, viral and bacterial products can trigger NK cell responses directly binding to surface TLR3 and TLR9 (16,17).…”