KLRG1: Difference between revisions

Jump to navigation Jump to search
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
imported>Sagreenberg
mNo edit summary
 
(One intermediate revision by one other user not shown)
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Killer cell lectin-like receptor subfamily G member 1''' is a [[protein]] that in humans is encoded by the ''KLRG1'' [[gene]].<ref name="Hanke_1999" /><ref name="Butcher_1998" /><ref name="Ito_2006" /><ref name="Thimme_2005" /><ref name="entrez" />
| update_page = yes
 
| require_manual_inspection = no
== Function ==
| update_protein_box = yes
 
| update_summary = yes
Natural killer (NK) cells are [[lymphocyte]]s 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.<ref name="entrez" />
| update_citations = yes
 
}}
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,<ref name="Nakamura_2009" /> respective markers of epithelial and mesenchymal cells.<ref name="Rosshart_2008" /> Targeting of other co-inhibitory receptors for applications in oncology has gained widespread interest<ref name="Pauken_2015" /><ref name="Mahoney_2015" /><ref name="Anderson_2016" /> (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,<ref name="Nishimura_1999" /><ref name="Tivol_1995" />  KLRG1 knockout mice initially were found to have no abnormal features,<ref name="Gründemann_2010" /> though were subsequently found to have enhanced immunity in a tuberculosis challenge model.<ref name="Cyktor_2013" />
 
The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers,<ref name="Melis_2014" /><ref name="Akbar_2011" /><ref name="Henson_2009" /> has contributed to relatively fewer studies on this molecule.
 
== References ==
{{reflist|refs =
 
<ref name="entrez">{{cite web | title = Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10219| access-date = }}</ref>
 
<ref name="Hanke_1999">{{cite journal | vauthors = Hanke T, Corral L, Vance RE, Raulet DH | title = 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 | journal = European Journal of Immunology | volume = 28 | issue = 12 | pages = 4409–17 | date = December 1998 | pmid = 9862378 | pmc =  | doi = 10.1002/(SICI)1521-4141(199812)28:12<4409::AID-IMMU4409>3.0.CO;2-3 }}</ref>
 
<ref name="Butcher_1998">{{cite journal | vauthors = Butcher S, Arney KL, Cook GP | title = MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells | journal = European Journal of Immunology | volume = 28 | issue = 11 | pages = 3755–62 | date = November 1998 | pmid = 9842918 | pmc =  | doi = 10.1002/(SICI)1521-4141(199811)28:11<3755::AID-IMMU3755>3.0.CO;2-3 }}</ref>
 
<ref name="Ito_2006">{{cite journal | vauthors = Ito M, Maruyama T, Saito N, Koganei S, Yamamoto K, Matsumoto N | title = Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity | journal = The Journal of Experimental Medicine | volume = 203 | issue = 2 | pages = 289–95 | date = February 2006 | pmid = 16461340 | pmc = 2118217 | doi = 10.1084/jem.20051986 }}</ref>
 
<ref name="Thimme_2005">{{cite journal | vauthors = Thimme R, Appay V, Koschella M, Panther E, Roth E, Hislop AD, Rickinson AB, Rowland-Jones SL, Blum HE, Pircher H | title = Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation | journal = Journal of Virology | volume = 79 | issue = 18 | pages = 12112–6 | date = September 2005 | pmid = 16140789 | pmc = 1212638 | doi = 10.1128/JVI.79.18.12112-12116.2005 }}</ref>
 
<ref name="Nakamura_2009">{{cite journal | vauthors = Nakamura S, Kuroki K, Ohki I, Sasaki K, Kajikawa M, Maruyama T, Ito M, Kameda Y, Ikura M, Yamamoto K, Matsumoto N, Maenaka K | title = Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1) | journal = The Journal of Biological Chemistry | volume = 284 | issue = 40 | pages = 27327–35 | date = October 2009 | pmid = 19654330 | pmc = 2785660 | doi = 10.1074/jbc.M109.038802 }}</ref>
 
<ref name="Rosshart_2008">{{cite journal | vauthors = Rosshart S, Hofmann M, Schweier O, Pfaff AK, Yoshimoto K, Takeuchi T, Molnar E, Schamel WW, Pircher H | title = Interaction of KLRG1 with E-cadherin: new functional and structural insights | journal = European Journal of Immunology | volume = 38 | issue = 12 | pages = 3354–64 | date = December 2008 | pmid = 19009530 | doi = 10.1002/eji.200838690 }}</ref>
 
<ref name="Pauken_2015">{{cite journal | vauthors = Pauken KE, Wherry EJ | title = Overcoming T cell exhaustion in infection and cancer | journal = Trends in Immunology | volume = 36 | issue = 4 | pages = 265–76 | date = April 2015 | pmid = 25797516 | doi = 10.1016/j.it.2015.02.008 }}</ref>
 
<ref name="Mahoney_2015">{{cite journal | vauthors = Mahoney KM, Rennert PD, Freeman GJ | title = Combination cancer immunotherapy and new immunomodulatory targets | journal = Nature Reviews. Drug Discovery | volume = 14 | issue = 8 | pages = 561–84 | date = August 2015 | pmid = 26228759 | doi = 10.1038/nrd4591 }}</ref>
 
<ref name="Anderson_2016">{{cite journal | vauthors = Anderson AC, Joller N, Kuchroo VK | title = Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation | journal = Immunity | volume = 44 | issue = 5 | pages = 989–1004 | date = May 2016 | pmid = 27192565 | pmc = 4942846 | doi = 10.1016/j.immuni.2016.05.001 }}</ref>
 
<ref name="Nishimura_1999">{{cite journal | vauthors = Nishimura H, Nose M, Hiai H, Minato N, Honjo T | title = Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor | journal = Immunity | volume = 11 | issue = 2 | pages = 141–51 | date = August 1999 | pmid = 10485649 | doi = | url = }}</ref>
 
<ref name="Tivol_1995">{{cite journal | vauthors = Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH | title = Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4 | journal = Immunity | volume = 3 | issue = 5 | pages = 541–7 | date = November 1995 | pmid = 7584144 | doi = | url = }}</ref>
 
<ref name="Gründemann_2010">{{cite journal | vauthors = Gründemann C, Schwartzkopff S, Koschella M, Schweier O, Peters C, Voehringer D, Pircher H | title = The NK receptor KLRG1 is dispensable for virus-induced NK and CD8+ T-cell differentiation and function in vivo | journal = European Journal of Immunology | volume = 40 | issue = 5 | pages = 1303–14 | date = May 2010 | pmid = 20201037 | doi = 10.1002/eji.200939771 }}</ref>
 
<ref name="Cyktor_2013">{{cite journal | vauthors = Cyktor JC, Carruthers B, Stromberg P, Flaño E, Pircher H, Turner J | title = Killer cell lectin-like receptor G1 deficiency significantly enhances survival after Mycobacterium tuberculosis infection | journal = Infection and Immunity | volume = 81 | issue = 4 | pages = 1090–9 | date = April 2013 | pmid = 23340310 | pmc = 3639586 | doi = 10.1128/IAI.01199-12 }}</ref>
 
<ref name="Melis_2014">{{cite journal | vauthors = Melis L, Van Praet L, Pircher H, Venken K, Elewaut D | title = 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 | journal = Annals of the Rheumatic Diseases | volume = 73 | issue = 6 | pages = 1223–31 | date = June 2014 | pmid = 23740233 | doi = 10.1136/annrheumdis-2013-203881 }}</ref>
 
<ref name="Akbar_2011">{{cite journal | vauthors = Akbar AN, Henson SM | title = Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? | journal = Nature Reviews. Immunology | volume = 11 | issue = 4 | pages = 289–95 | date = April 2011 | pmid = 21436838 | doi = 10.1038/nri2959 }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
<ref name="Henson_2009">{{cite journal | vauthors = Henson SM, Akbar AN | title = KLRG1--more than a marker for T cell senescence | journal = Age (Dordrecht, Netherlands) | volume = 31 | issue = 4 | pages = 285–91 | date = December 2009 | pmid = 19479342 | pmc = 2813054 | doi = 10.1007/s11357-009-9100-9 }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Killer cell lectin-like receptor subfamily G, member 1
| HGNCid = 6380
| Symbol = KLRG1
| AltSymbols =; 2F1; CLEC15A; MAFA; MAFA-2F1; MAFA-L; MGC13600
| OMIM = 604874
| ECnumber = 
| Homologene = 4244
| MGIid = 1355294
| GeneAtlas_image1 = PBB_GE_KLRG1_210288_at_tn.png
| Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005529 |text = sugar binding}}
| Component = {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006968 |text = cellular defense response}} {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10219
    | Hs_Ensembl = ENSG00000139187
    | Hs_RefseqProtein = NP_005801
    | Hs_RefseqmRNA = NM_005810
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 9033484
    | Hs_GenLoc_end = 9054605
    | Hs_Uniprot = 
    | Mm_EntrezGene = 50928
    | Mm_Ensembl = ENSMUSG00000030114
    | Mm_RefseqmRNA = NM_016970
    | Mm_RefseqProtein = NP_058666
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 122236213
    | Mm_GenLoc_end = 122248452
    | Mm_Uniprot = 
  }}
}}
'''Killer cell lectin-like receptor subfamily G, member 1''', also known as '''KLRG1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10219| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = 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. Alternatively spliced transcript variants have been reported, but their full-length natures have not yet been determined.<ref name="entrez">{{cite web | title = Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10219| accessdate = }}</ref>
}}
}}


==References==
== Further reading ==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Ortega E, Schneider H, Pecht I | title = Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen | journal = International Immunology | volume = 3 | issue = 4 | pages = 333–42 | date = April 1991 | pmid = 1831652 | doi = 10.1093/intimm/3.4.333 }}
| citations =
* {{cite journal | vauthors = Lamers MB, Lamont AG, Williams DH | title = Human MAFA has alternatively spliced variants | journal = Biochimica et Biophysica Acta | volume = 1399 | issue = 2-3 | pages = 209–12 | date = August 1998 | pmid = 9765598 | doi = 10.1016/s0167-4781(98)00107-9 }}
*{{cite journal | author=Ortega E, Schneider H, Pecht I |title=Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen. |journal=Int. Immunol. |volume=3 |issue= 4 |pages= 333-42 |year= 1991 |pmid= 1831652 |doi= }}
* {{cite journal | vauthors = Voehringer D, Koschella M, Pircher H | title = Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1) | journal = Blood | volume = 100 | issue = 10 | pages = 3698–702 | date = November 2002 | pmid = 12393723 | doi = 10.1182/blood-2002-02-0657 }}
*{{cite journal | author=Lamers MB, Lamont AG, Williams DH |title=Human MAFA has alternatively spliced variants. |journal=Biochim. Biophys. Acta |volume=1399 |issue= 2-3 |pages= 209-12 |year= 1998 |pmid= 9765598 |doi= }}
* {{cite journal | vauthors = Matsuoka TA, Artner I, Henderson E, Means A, Sander M, Stein R | title = The MafA transcription factor appears to be responsible for tissue-specific expression of insulin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 9 | pages = 2930–3 | date = March 2004 | pmid = 14973194 | pmc = 365722 | doi = 10.1073/pnas.0306233101 }}
*{{cite journal  | author=Butcher S, Arney KL, Cook GP |title=MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells. |journal=Eur. J. Immunol. |volume=28 |issue= 11 |pages= 3755-62 |year= 1998 |pmid= 9842918 |doi=  }}
* {{cite journal | vauthors = Marcolino I, Przybylski GK, Koschella M, Schmidt CA, Voehringer D, Schlesier M, Pircher H | title = Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history | journal = European Journal of Immunology | volume = 34 | issue = 10 | pages = 2672–80 | date = October 2004 | pmid = 15368283 | doi = 10.1002/eji.200425282 }}
*{{cite journal  | author=Hanke T, Corral L, Vance RE, Raulet DH |title=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. |journal=Eur. J. Immunol. |volume=28 |issue= 12 |pages= 4409-17 |year= 1999 |pmid= 9862378 |doi=  }}
* {{cite journal | vauthors = Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP | title = 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 = Journal of Immunology | volume = 174 | issue = 10 | pages = 6088–94 | date = May 2005 | pmid = 15879103 | doi = 10.4049/jimmunol.174.10.6088 }}
*{{cite journal | author=Voehringer D, Koschella M, Pircher H |title=Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). |journal=Blood |volume=100 |issue= 10 |pages= 3698-702 |year= 2003 |pmid= 12393723 |doi= 10.1182/blood-2002-02-0657 }}
* {{cite journal | vauthors = 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 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Bengsch B, Spangenberg HC, Kersting N, Neumann-Haefelin C, Panther E, von Weizsäcker F, Blum HE, Pircher H, Thimme R | title = 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 = Journal of Virology | volume = 81 | issue = 2 | pages = 945–53 | date = January 2007 | pmid = 17079288 | pmc = 1797464 | doi = 10.1128/JVI.01354-06 }}
*{{cite journal  | author=Matsuoka TA, Artner I, Henderson E, ''et al.'' |title=The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 9 |pages= 2930-3 |year= 2004 |pmid= 14973194 |doi= 10.1073/pnas.0306233101 }}
* {{cite journal | vauthors = Schwartzkopff S, Gründemann C, Schweier O, Rosshart S, Karjalainen KE, Becker KF, Pircher H | title = Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans | journal = Journal of Immunology | volume = 179 | issue = 2 | pages = 1022–9 | date = July 2007 | pmid = 17617594 | doi = 10.4049/jimmunol.179.2.1022 }}
*{{cite journal | author=Marcolino I, Przybylski GK, Koschella M, ''et al.'' |title=Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history. |journal=Eur. J. Immunol. |volume=34 |issue= 10 |pages= 2672-80 |year= 2004 |pmid= 15368283 |doi= 10.1002/eji.200425282 }}
*{{cite journal | author=Ibegbu CC, Xu YX, Harris W, ''et al.'' |title=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=J. Immunol. |volume=174 |issue= 10 |pages= 6088-94 |year= 2005 |pmid= 15879103 |doi=  }}
*{{cite journal  | author=Thimme R, Appay V, Koschella M, ''et al.'' |title=Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. |journal=J. Virol. |volume=79 |issue= 18 |pages= 12112-6 |year= 2005 |pmid= 16140789 |doi= 10.1128/JVI.79.18.12112-12116.2005 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal | author=Ito M, Maruyama T, Saito N, ''et al.'' |title=Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. |journal=J. Exp. Med. |volume=203 |issue= 2 |pages= 289-95 |year= 2006 |pmid= 16461340 |doi= 10.1084/jem.20051986 }}
*{{cite journal  | author=Bengsch B, Spangenberg HC, Kersting N, ''et al.'' |title=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=J. Virol. |volume=81 |issue= 2 |pages= 945-53 |year= 2007 |pmid= 17079288 |doi= 10.1128/JVI.01354-06 }}
*{{cite journal | author=Schwartzkopff S, Gründemann C, Schweier O, ''et al.'' |title=Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans. |journal=J. Immunol. |volume=179 |issue= 2 |pages= 1022-9 |year= 2007 |pmid= 17617594 |doi= }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* {{UCSC genome browser|KLRG1}}
* {{UCSC gene details|KLRG1}}
 
 
 
{{gene-12-stub}}

Latest revision as of 04:10, 11 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.[1][2][3][4][5]

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.[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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 5.0 5.1 "Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1".
  6. 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.
  7. 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.
  8. 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. PMID 25797516.
  9. 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.
  10. 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.
  11. 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. PMID 10485649.
  12. 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. PMID 7584144.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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

External links