KLRG1

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.[5][6][7][8][9]

KLRG1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKLRG1, 2F1, CLEC15A, MAFA, MAFA-2F1, MAFA-L, MAFA-LIKE, killer cell lectin like receptor G1
External IDsOMIM: 604874 MGI: 1355294 HomoloGene: 4244 GeneCards: KLRG1
Orthologs
SpeciesHumanMouse
Entrez

10219

50928

Ensembl

ENSG00000139187

ENSMUSG00000030114

UniProt

Q96E93

O88713

RefSeq (mRNA)

NM_001329099
NM_001329101
NM_001329102
NM_001329103
NM_005810

NM_016970

RefSeq (protein)

NP_001316028
NP_001316030
NP_001316031
NP_001316032
NP_005801

NP_058666

Location (UCSC)Chr 12: 8.95 – 9.01 MbChr 6: 122.25 – 122.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.

References
  1. GRCh38: Ensembl release 89: ENSG00000139187 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030114 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hanke T, Corral L, Vance RE, Raulet DH (December 1998). "2F1 antigen, the mouse homolog of the rat "mast cell function-associated antigen", is a lectin-like type II transmembrane receptor expressed by natural killer cells". European Journal of Immunology. 28 (12): 4409–17. doi:10.1002/(SICI)1521-4141(199812)28:12<4409::AID-IMMU4409>3.0.CO;2-3. PMID 9862378.
  6. Butcher S, Arney KL, Cook GP (November 1998). "MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells". European Journal of Immunology. 28 (11): 3755–62. doi:10.1002/(SICI)1521-4141(199811)28:11<3755::AID-IMMU3755>3.0.CO;2-3. PMID 9842918.
  7. Ito M, Maruyama T, Saito N, Koganei S, Yamamoto K, Matsumoto N (February 2006). "Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity". The Journal of Experimental Medicine. 203 (2): 289–95. doi:10.1084/jem.20051986. PMC 2118217. PMID 16461340.
  8. Thimme R, Appay V, Koschella M, Panther E, Roth E, Hislop AD, Rickinson AB, Rowland-Jones SL, Blum HE, Pircher H (September 2005). "Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation". Journal of Virology. 79 (18): 12112–6. doi:10.1128/JVI.79.18.12112-12116.2005. PMC 1212638. PMID 16140789.
  9. "Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1".
  10. Nakamura S, Kuroki K, Ohki I, Sasaki K, Kajikawa M, Maruyama T, Ito M, Kameda Y, Ikura M, Yamamoto K, Matsumoto N, Maenaka K (October 2009). "Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)". The Journal of Biological Chemistry. 284 (40): 27327–35. doi:10.1074/jbc.M109.038802. PMC 2785660. PMID 19654330.
  11. Rosshart S, Hofmann M, Schweier O, Pfaff AK, Yoshimoto K, Takeuchi T, Molnar E, Schamel WW, Pircher H (December 2008). "Interaction of KLRG1 with E-cadherin: new functional and structural insights". European Journal of Immunology. 38 (12): 3354–64. doi:10.1002/eji.200838690. PMID 19009530. S2CID 21597777.
  12. Pauken KE, Wherry EJ (April 2015). "Overcoming T cell exhaustion in infection and cancer". Trends in Immunology. 36 (4): 265–76. doi:10.1016/j.it.2015.02.008. PMC 4393798. PMID 25797516.
  13. 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. PMID 26228759. S2CID 2220735.
  14. Anderson AC, Joller N, Kuchroo VK (May 2016). "Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation". Immunity. 44 (5): 989–1004. doi:10.1016/j.immuni.2016.05.001. PMC 4942846. PMID 27192565.
  15. Nishimura H, Nose M, Hiai H, Minato N, Honjo T (August 1999). "Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor". Immunity. 11 (2): 141–51. doi:10.1016/s1074-7613(00)80089-8. PMID 10485649.
  16. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH (November 1995). "Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4". Immunity. 3 (5): 541–7. doi:10.1016/1074-7613(95)90125-6. PMID 7584144.
  17. Gründemann C, Schwartzkopff S, Koschella M, Schweier O, Peters C, Voehringer D, Pircher H (May 2010). "The NK receptor KLRG1 is dispensable for virus-induced NK and CD8+ T-cell differentiation and function in vivo". European Journal of Immunology. 40 (5): 1303–14. doi:10.1002/eji.200939771. PMID 20201037.
  18. Cyktor JC, Carruthers B, Stromberg P, Flaño E, Pircher H, Turner J (April 2013). "Killer cell lectin-like receptor G1 deficiency significantly enhances survival after Mycobacterium tuberculosis infection". Infection and Immunity. 81 (4): 1090–9. doi:10.1128/IAI.01199-12. PMC 3639586. PMID 23340310.
  19. 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. PMID 23740233. S2CID 206850050.
  20. 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. PMID 21436838. S2CID 13364819.
  21. Henson SM, Akbar AN (December 2009). "KLRG1--more than a marker for T cell senescence". Age (Dordrecht, Netherlands). 31 (4): 285–91. doi:10.1007/s11357-009-9100-9. PMC 2813054. PMID 19479342.

Further reading


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