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.[5]
KLRG1 is a lymphocyte co-inhibitory, or immune checkpoint, receptor expressed predominantly on late-differentiated effector and effector memory CD8+ T and NK cells. It’s ligands are E-cadherin and N-cadherin with similar affinities,[6] respective markers of epithelial and mesenchymal cells.[7] Targeting of other co-inhibitory receptors for applications in oncology has gained widespread interest[8][9][10] (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,[11][12] KLRG1 knockout mice initially were found to have no abnormal features,[13] though were subsequently found to have enhanced immunity in a tuberculosis challenge model.[14]
The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers,[15][16][17] has contributed to relatively fewer studies on this molecule.
References
↑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. PMID9862378.
↑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. PMID19009530.
↑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. PMID25797516.
↑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.
↑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. PMID10485649.
↑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. PMID7584144.
↑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. PMID20201037.
↑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.
↑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.
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. 1399 (2–3): 209–12. doi:10.1016/s0167-4781(98)00107-9. PMID9765598.
Voehringer D, Koschella M, Pircher H (November 2002). "Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)". Blood. 100 (10): 3698–702. doi:10.1182/blood-2002-02-0657. PMID12393723.
Marcolino I, Przybylski GK, Koschella M, Schmidt CA, Voehringer D, Schlesier M, Pircher H (October 2004). "Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history". European Journal of Immunology. 34 (10): 2672–80. doi:10.1002/eji.200425282. PMID15368283.
Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP (May 2005). "Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57". Journal of Immunology. 174 (10): 6088–94. doi:10.4049/jimmunol.174.10.6088. PMID15879103.
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. doi:10.1038/nature04209. PMID16189514.
