About KLR / Killer Cell Lectin-like Receptor:
Killer cell lectin-like receptor G1 (KLRG1) is a lectin-like inhibitory receptor that belongs to the C-type. It can be found anywhere from 50% to 80% of human NK cells. Following a virus or parasite infection, the expression of KLRG1 is significantly increased. The biological ligand for KLRG is E-cadherin. In adherents junctions, E-cadherin creates a close bond between neighbouring epithelial cells.
The number 136 E-cadherin has five extracellular domains (EC1–EC5) that are similar to Ig. KLRG1 also recognizes n- and R-cadherins. The binding of E-cadherin to KLRG1 protects tissue from damage by preventing KLRG1+ NK cells from lysing E-cadherin-expressing epithelial cells. KLRG1 can also play a role in tumour immunosurveillance by detecting epithelial tumours with decreased E-cadherin expression, indicating that they are metastatic. One KLRG1 CTLD engages one EC1 molecule in the structure of KLRG1 bound to the EC1 domain of E-cadherin.
Killer Cell Lectin-like Receptor Mechanism
KLRG1 recognizes its non-MHC ligand in the same way that Ly49 recognizes MHC-I, with each CTLD subunit containing an entire ligand-binding site. NKG2D and MICA117, on the other hand, bind to a site formed by two CTLD monomers. E-cadherin binds to a ligand-binding site on the surface of KLRG1 that is similar to that of Ly49s and other C-type lectin-like NK receptors. KLRG1 mainly interacts with E-cadherin residues Val3-Ile7, which are highly conserved in E-, N-, and R-cadherins. Consequently, NK cells with a single KLRG1 receptor can monitor the expression of different cadherins on target cells.
KLRK1 activation causes phosphorylation of vav guanine nucleotide exchange factor 1 (VAV1), which leads to actin-dependent clustering of stimulatory receptors and recruitment to lipid rafts. This causes further VAV1 phosphorylation, triggering a positive feedback loop that results in the release of arachidonic acids by intraepithelial cytotoxic T lymphocytes. They can then cause granulocyte activation and inflammation in the intestine.