KLRG1 explained

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.

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.

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, respective markers of epithelial and mesenchymal cells. Targeting of other co-inhibitory receptors for applications in oncology has gained widespread interest (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, KLRG1 knockout mice initially were found to have no abnormal features, though were subsequently found to have enhanced immunity in a tuberculosis challenge model.

The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers, has contributed to relatively fewer studies on this molecule.

Further reading

• Ortega E, Schneider H, Pecht I . Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen . International Immunology . 3 . 4 . 333–42 . April 1991 . 1831652 . 10.1093/intimm/3.4.333 .
• Lamers MB, Lamont AG, Williams DH . Human MAFA has alternatively spliced variants . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1399 . 2–3 . 209–12 . August 1998 . 9765598 . 10.1016/s0167-4781(98)00107-9 .
• Voehringer D, Koschella M, Pircher H . Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1) . Blood . 100 . 10 . 3698–702 . November 2002 . 12393723 . 10.1182/blood-2002-02-0657 . free .
• Matsuoka TA, Artner I, Henderson E, Means A, Sander M, Stein R . The MafA transcription factor appears to be responsible for tissue-specific expression of insulin . Proceedings of the National Academy of Sciences of the United States of America . 101 . 9 . 2930–3 . March 2004 . 14973194 . 365722 . 10.1073/pnas.0306233101 . 2004PNAS..101.2930M . free .
• Marcolino I, Przybylski GK, Koschella M, Schmidt CA, Voehringer D, Schlesier M, Pircher H . 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 . October 2004 . 15368283 . 10.1002/eji.200425282 . 8599066 . free .
• Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP . 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 . May 2005 . 15879103 . 10.4049/jimmunol.174.10.6088 . free .
• 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Bengsch B, Spangenberg HC, Kersting N, Neumann-Haefelin C, Panther E, von Weizsäcker F, Blum HE, Pircher H, Thimme R . Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell subsets in the peripheral blood and liver . Journal of Virology . 81 . 2 . 945–53 . January 2007 . 17079288 . 1797464 . 10.1128/JVI.01354-06 .
• Schwartzkopff S, Gründemann C, Schweier O, Rosshart S, Karjalainen KE, Becker KF, Pircher H . Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans . Journal of Immunology . 179 . 2 . 1022–9 . July 2007 . 17617594 . 10.4049/jimmunol.179.2.1022 . free .