Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules.[9]
KLRG1 is a lymphocyte co-inhibitory, or immune checkpoint, receptor expressed predominantly on late-differentiated effector and effector memory CD8+ T and NK cells. Its ligands are E-cadherin and N-cadherin with similar affinities,[10] respective markers of epithelial and mesenchymal cells.[11] Targeting of other co-inhibitory receptors for applications in oncology has gained widespread interest[12][13][14] (e.g., CTLA-4, PD-1, and its ligand PD-L1). Unlike the obvious enhanced immune activation present in CTLA-4 and PD-1 gene knockout mice,[15][16] KLRG1 knockout mice initially were found to have no abnormal features,[17] though were subsequently found to have enhanced immunity in a tuberculosis challenge model.[18]
The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers,[19][20][21] has contributed to relatively fewer studies on this molecule.
^Mahoney KM, Rennert PD, Freeman GJ (August 2015). "Combination cancer immunotherapy and new immunomodulatory targets". Nature Reviews. Drug Discovery. 14 (8): 561–84. doi:10.1038/nrd4591. PMID26228759. S2CID2220735.
^Melis L, Van Praet L, Pircher H, Venken K, Elewaut D (June 2014). "Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints". Annals of the Rheumatic Diseases. 73 (6): 1223–31. doi:10.1136/annrheumdis-2013-203881. PMID23740233. S2CID206850050.
^Akbar AN, Henson SM (April 2011). "Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?". Nature Reviews. Immunology. 11 (4): 289–95. doi:10.1038/nri2959. PMID21436838. S2CID13364819.
Ortega E, Schneider H, Pecht I (April 1991). "Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen". International Immunology. 3 (4): 333–42. doi:10.1093/intimm/3.4.333. PMID1831652.
Lamers MB, Lamont AG, Williams DH (August 1998). "Human MAFA has alternatively spliced variants". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1399 (2–3): 209–12. doi:10.1016/s0167-4781(98)00107-9. PMID9765598.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID16189514. S2CID4427026.
Overview of all the structural information available in the PDB for UniProt: Q96E93 (Killer cell lectin-like receptor subfamily G member 1) at the PDBe-KB.
