Skip to main content
SpringerLink
Log in

KLRC4, KLRG1, and Natural Cytotoxicity Receptors

  • Chapter
  • First Online:
Animal Lectins: Form, Function and Clinical Applications

  • 1527 Accesses

Abstract

In earlier Chapters we discussed mouse and human NK cell lectin receptors which can deliver inhibitory or activatory NK cell cytotoxicity in presence or absence of MHC-I molecules. Among non-lectin inhibitory receptors, killer immunoglobulin (Ig)-like receptors (KIRs) recognize different allelic groups of HLA-A, -B or -C molecules. ILT2 (or LIR-1) receptors are more ‘promiscuous’, as they recognize a large number of HLA class I alleles, while CRD containing CD94-NKG2A recognizes HLA-E, an HLA class I molecule with a limited polymorphism. It is well known that various HLA class I alleles provide signal sequence peptides that bind HLA-E and enable it to be expressed on the cell surface. Importantly, each type of KIR is expressed only by a subset of NK cells (Braud et al. 1998). A common characteristic of the various HLA class I-specific inhibitory receptors is the presence, in their cytoplasmic tail, of ITIM that enable them to recruit and activate SHP-1 and SHP-2 phosphatases (Moretta et al. 2001; Lanier 1998). In turn, these phosphatases switch off the activating signaling cascade initiated by the various activating receptors (Moretta and Moretta 2004). In this chapter we continue discussing cytotoxic receptors which do not depend on HLA antigens for their action and do not contain ITIM motif in their cytoplasmic tail as well as activating NK cell receptors which are of recent origin but do not contain lectin-like domain till date.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abramson J, Xu R, Pecht I (2002) An unusual inhibitory receptor–the mast cell function-associated antigen (MAFA). Mol Immunol 38:1307–1313

    Article  PubMed  CAS  Google Scholar 

  • Abramson J, Licht A, Pecht I (2006) Selective inhibition of the FcεRI-induced de novo synthesis of mediators by an inhibitory receptor. EMBO J 25:323–334

    Article  PubMed  CAS  Google Scholar 

  • Barisas BG, Smith SM, Liu J et al (2007) Compartmentalization of the Type I Fc ε receptor and MAFA on mast cell membranes. Biophys Chem 126:209–217

    Article  PubMed  CAS  Google Scholar 

  • Bengsch B, Spangenberg HC, Kersting N et al (2007) 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. J Virol 81:945–953

    Article  PubMed  CAS  Google Scholar 

  • Beyersdorf NB, Ding X, Karp K, Hanke T (2001) Expression of inhibitory “killer cell lectin-like receptor G1” identifies unique subpopulations of effector and memory CD8 T cells. Eur J Immunol 31:3443–3452

    Article  PubMed  CAS  Google Scholar 

  • Beyersdorf N, Ding X, Tietze JK et al (2007) Characterization of mouse CD4 T cell subsets defined by expression of KLRG1. Eur J Immunol 37:3445–3454

    Article  PubMed  CAS  Google Scholar 

  • Biassoni R, Cantoni C, Pende D et al (2001) Human natural killer cell receptors and co-receptors. Immunol Rev 181:203–214

    Article  PubMed  CAS  Google Scholar 

  • Biassoni R, Fogli M, Cantoni C et al (2005) Molecular and functional characterization of NKG2D, NKp80, and NKG2C triggering NK cell receptors in rhesus and cynomolgus macaques: monitoring of NK cell function during simian HIV infection. J Immunol 174:5695–5705

    PubMed  CAS  Google Scholar 

  • Binsack R, Pecht I (1997) The mast cell function-associated antigen exhibits saccharide binding capacity. Eur J Immunol 27:2557–2561

    Article  PubMed  CAS  Google Scholar 

  • Blaser C, Kaufmann M, Pircher H (1998) Virus-activated CD8 T cells and lymphokine-activated NK cells express the mast cell function-associated antigen, an inhibitory C-type lectin. J Immunol 161:6451–6454

    PubMed  CAS  Google Scholar 

  • Bocek P Jr, Guthmann MD, Pecht I (1997) Analysis of the genes encoding the mast cell function-associated antigen and its alternatively spliced transcripts. J Immunol 158:3235–3243

    PubMed  CAS  Google Scholar 

  • Braud VM, Allan DS, O’Callaghan CA et al (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391:795–799

    Article  PubMed  CAS  Google Scholar 

  • Butcher S, Arney KL, Cook GP (1998) MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells. Eur J Immunol 28:3755–3762

    Article  PubMed  CAS  Google Scholar 

  • Cagnano E, Hershkovitz O, Zilka A et al (2008) Expression of ligands to NKp46 in benign and malignant melanocytes. J Invest Dermatol 128:972–979

    Article  PubMed  CAS  Google Scholar 

  • Cantoni C, Bottino C, Vitale M et al (1999) NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J Exp Med 189:787–796

    Article  PubMed  CAS  Google Scholar 

  • Cohen-Dayag A, Schneider H, Pecht I (1992) Variants of the mucosal mast cell line (RBL-2H3) deficient in a functional membrane glycoprotein. Immunobiology 185:124–149

    Article  PubMed  CAS  Google Scholar 

  • Corral L, Hanke T, Vance RE et al (2000) NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules. Eur J Immunol 30:920–930

    Article  PubMed  CAS  Google Scholar 

  • Costello RT, Sivori S, Marcenaro E et al (2002) Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood 99:3661–3667

    Article  PubMed  CAS  Google Scholar 

  • De Celis R, Feria-Velasco A, Bravo-Cuellar A et al (2008) Expression of NK cells activation receptors after occupational exposure to toxics: a preliminary study. Immunol Lett 118:125–131

    Article  PubMed  Google Scholar 

  • Dennehy KM, Klimosch SN, Steinle A (2011) NKp80 uses an atypical hemi-ITAM to trigger NK cytotoxicity. J Immunol 186:657–661

    Article  PubMed  CAS  Google Scholar 

  • Eberl M, Engel R, Aberle S et al (2005) Human Vγ9/Vδ2 effector memory T cells express the killer cell lectin-like receptor G1 (KLRG1). J Leukoc Biol 77:67–70

    PubMed  CAS  Google Scholar 

  • Garcia-Iglesias T, Del Toro-Arreola A et al (2009) Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer 9:186

    Article  PubMed  Google Scholar 

  • Gründemann C, Bauer M, Schweier O et al (2006) Cutting edge: identification of E-cadherin as a ligand for the murine killer cell lectin-like receptor G1. J Immunol 176:1311–1315

    PubMed  Google Scholar 

  • Guthmann MD, Tal M, Pecht I (1995a) A new member of the C-type lectin family is a modulator of the mast cell secretory response. Int Arch Allergy Immunol 107:82–86

    Article  PubMed  CAS  Google Scholar 

  • Guthmann MD, Tal M, Pecht I (1995b) A secretion inhibitory signal transduction molecule on mast cells is another C-type lectin. Proc Natl Acad Sci USA 92:9397–9401

    Article  PubMed  CAS  Google Scholar 

  • Hamann J, Montgomery KT, Lau S et al (1997) AICL: a new activation-induced antigen encoded by the human NK gene complex. Immunogenetics 45:295–300

    Article  PubMed  CAS  Google Scholar 

  • Han Y, Zhang M, Li N et al (2004) KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity. Blood 104:2858–2866, KLR

    Article  PubMed  CAS  Google Scholar 

  • Hanke T, Corral L, Vance RE, Raulet DH (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. Eur J Immunol 28:4409–4417

    Article  PubMed  CAS  Google Scholar 

  • Huntington ND, Tabarias H, Fairfax K et al (2007) NK cell maturation and peripheral homeostasis is associated with KLRG1 up-regulation. J Immunol 178:4764–4770

    PubMed  CAS  Google Scholar 

  • Ibegbu CC, Xu Y-X, Harris W et al (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. J Immunol 174:6088–6094

    PubMed  CAS  Google Scholar 

  • Ito M, Maruyama T, Saito N et al (2006) Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. J Expt Med 203:289–295

    Article  Google Scholar 

  • Ito K, Higai K, Sakurai M et al (2011) Binding of natural cytotoxicity receptor NKp46 to sulfate- and α2,3-NeuAc-containing glycans and its mutagenesis. Biochem Biophys Res Commun 406:377–382

    Article  PubMed  CAS  Google Scholar 

  • Jürgens L, Arndt-Jovin D, Pecht I, Jovin TM (1996) Proximity relationships between the type I receptor for Fc ε (FcεRI) and the mast cell function-associated antigen (MAFA) studied by donor photobleaching fluorescence resonance energy transfer microscopy. Eur J Immunol 26:84–91

    Article  PubMed  Google Scholar 

  • Kamimura D, Bevan MJ (2008) Endoplasmic reticulum stress regulator XBP-1 contributes to effector CD8+ T cell differentiation during acute infection. J Immunol 181:5433–5441

    PubMed  CAS  Google Scholar 

  • Kim DK, Kabat J, Borrego F et al (2004) Human NKG2F is expressed and can associate with DAP12. Mol Immunol 41:53–62

    Article  PubMed  CAS  Google Scholar 

  • Koike J, Wakao H, Ishizuka Y et al (2004) Bone marrow allograft rejection mediated by a novel murine NK receptor, NKG2I. J Exp Med 199:137–144

    Article  PubMed  CAS  Google Scholar 

  • Kuttruff S, Koch S, Kelp A et al (2009) NKp80 defines and stimulates a reactive subset of CD8 T cells. Blood 113:358–369

    Article  PubMed  CAS  Google Scholar 

  • Lamers MBAC, Lamont AG, Williams DH (1998) Human MAFA has alternatively spliced variants. Biochim Biophys Acta 1399:209–212. doi:dx.doi.org

    Article  PubMed  CAS  Google Scholar 

  • Lanier LL (1998) NK receptors. Annu Rev Immunol 16:359–393

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Hofmann M, Wang Q et al (2009) Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity 31:35–46

    Article  PubMed  Google Scholar 

  • Licht A, Pecht I, Schweitzer-Stenner R (2005) Regulation of mast cells’ secretory response by co-clustering the Type 1 Fcε receptor with the mast cell function-associated antigen. Eur J Immunol 35:1621–1633

    Article  PubMed  CAS  Google Scholar 

  • Licht A, Abramson J, Pecht I (2006) Co-clustering activating and inhibitory receptors: impact at varying expression levels of the latter. Immunol Lett 104:166–170

    Article  PubMed  CAS  Google Scholar 

  • Magri G, Muntasell A, Romo N et al (2011) NKp46 and DNAM-1 NK-cell receptors drive the response to human cytomegalovirus-infected myeloid dendritic cells overcoming viral immune evasion strategies. Blood 117:848–856

    Article  PubMed  CAS  Google Scholar 

  • Marcolino I, Przybylski GK, Koschella M et al (2004) Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history. Eur J Immunol 34:2672–2680

    Article  PubMed  CAS  Google Scholar 

  • Mavilio D, Benjamin J, Kim D et al (2005) Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys. Blood 106:1718–1725

    Article  PubMed  CAS  Google Scholar 

  • McMahon CW, Zajac AJ, Jamieson AM et al (2002) Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8+ T cells. J Immunol 169:1444–1452

    PubMed  CAS  Google Scholar 

  • Moretta A (2002) Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2:957–965

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Bottino C, Millo R, Biassoni R (1999) HLA-specific and non-HLA-specific human NK receptors. Curr Top Microbiol Immunol 244:69–84

    Article  PubMed  CAS  Google Scholar 

  • Moretta L, Moretta A (2004) Unravelling natural killer cell function: triggering and inhibitory human NK receptors. EMBO J 23:255–259

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Biassoni R, Bottino C et al (2000) Natural cytotoxicity receptors that trigger human NK-mediated cytolysis. Immunol Today 21:228–234

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Bottino C, Vitale M et al (2001) Activating receptors and co-receptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  PubMed  CAS  Google Scholar 

  • Ortega E, Schneider H, Pecht I (1991) Possible interactions between the Fc ε receptor and a novel mast cell function-associated antigen. Int Immunol 3:333–342

    Article  PubMed  CAS  Google Scholar 

  • Ouyang Q, Wagner WM, Voehringer D et al (2003) Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). Exp Gerontol 38:911–920

    Article  PubMed  CAS  Google Scholar 

  • Pende D, Parolini S, Pessino A et al (1999) Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med 190:1505–1516

    Article  PubMed  CAS  Google Scholar 

  • Pende D, Rivera P, Marcenaro S et al (2002) Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell citotoxicity. Cancer Res 62:6178–6186

    PubMed  CAS  Google Scholar 

  • Pessino A, Sivori S, Bottino C et al (1998) Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med 188:953–960

    Article  PubMed  CAS  Google Scholar 

  • Plougastel B, Trowsdale J (1998a) Cloning of NKG2-F, A new member of the NKG2 family of human natural killer cell receptor genes. Eur J Immunol 27:2835–2839

    Article  Google Scholar 

  • Plougastel B, Trowsdale J (1998b) Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. Genomics 49:193–199

    Article  PubMed  CAS  Google Scholar 

  • Renedo M, Arce I, Montgomery K et al (2000) A sequence-ready physical map of the region containing the human natural killer gene complex on chromosome 12p12.3-p13.2. Genomics 65:129–136

    Article  PubMed  CAS  Google Scholar 

  • Robbins SH, Nguyen KB, Takahashi N et al (2002) Cutting edge: Inhibitory functions of the killer cell lectin-like receptor G1 molecule during the activation of mouse NK cells. J Immunol 168:2585–2589

    PubMed  CAS  Google Scholar 

  • Robbins SH, Terrizzi SC, Sydora BC et al (2003) Differential regulation of killer cell lectin-like receptor G1 expression on T cells. J Immunol 170:5876–5885

    PubMed  CAS  Google Scholar 

  • Roda-Navarro P, Arce I, Renedo M et al (2000) Human KLRF1, a novel member of the killer cell lectin-like receptor gene family: molecular characterization, genomic structure, physical mapping to the NK gene complex and expression analysis. Eur J Immunol 30:568–576

    Article  PubMed  CAS  Google Scholar 

  • Roda-Navarro P, Hernanz-Falcón P, Arce I et al (2001) Molecular characterization of two novel alternative spliced variants of the KLRF1 gene and subcellular distribution of KLRF1 isoforms. Biochim Biophys Acta 1520:141–146

    Article  PubMed  CAS  Google Scholar 

  • Rubinstein MP, Lind NA, Purton JF et al (2008) IL-7 and IL-15 differentially regulate CD8+ T cell subsets during contraction of the immune response. Blood 112:3704–3712

    Article  PubMed  CAS  Google Scholar 

  • Rutjens E, Mazza S, Biassoni R et al (2007) Differential NKp30 inducibility in chimpanzee NK cells and conserved NK cell phenotype and function in long-term HIV-1-infected animals. J Immunol 178:1702–1712

    PubMed  CAS  Google Scholar 

  • Saether PC, Westgaard IH, Hoelsbrekken SE et al (2008) KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that inversely regulate NK cell cytotoxicity. J Immunol 181:3177–3182

    PubMed  CAS  Google Scholar 

  • Schwartzkopff S, Gründemann C, Schweier O et al (2007) Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans. J Immunol 179:1022–1029

    PubMed  CAS  Google Scholar 

  • Schweitzer-Stenner R, Engelke M, Licht A, Pecht I (1999) Mast cell stimulation by co-clustering the type I Fc ε-receptors with mast cell function-associated antigens. Immunol Lett 68:71–78

    Article  PubMed  CAS  Google Scholar 

  • Shimizu E, Koike J, Wakao H et al (2004) Role of a NK receptor, KLRE-1, in bone marrow allograft rejection: analysis with KLRE-1-deficient mice. Blood 104:781–783

    Article  PubMed  CAS  Google Scholar 

  • Simpson RJ, Florida-James GD, Cosgrove C et al (2007) High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects. J Appl Physiol 103:396–401

    Article  PubMed  CAS  Google Scholar 

  • Simpson RJ, Cosgrove C, Ingram LA et al (2008) Senescent T-lymphocytes are mobilised into the peripheral blood compartment in young and older humans after exhaustive exercise. Brain Behav Immun 22:544–551

    Article  PubMed  CAS  Google Scholar 

  • Sivori S, Vitale M, Morelli L et al (1997) p46, a novel natural killer cell-specific. J Exp Med 186:1129–1136

    Article  PubMed  CAS  Google Scholar 

  • Sivori S, Parolini S, Falco M et al (2000) 2B4 functions as a co-receptor in human natural killer cell activation. Eur J Immunol 30:787–793

    Article  PubMed  CAS  Google Scholar 

  • Song J, Hagen GM, Roess DA et al (2002) The mast cell function-associated antigen and its interactions with the type I Fcε receptor. Biochemistry 41:881–889

    Article  PubMed  CAS  Google Scholar 

  • Stubbe M, Vanderheyde N, Pircher H et al (2008) Characterization of a subset of antigen-specific human central memory CD4+ T lymphocytes producing effector cytokines. Eur J Immunol 38:273–282

    Article  PubMed  CAS  Google Scholar 

  • Tessmer MS, Fugere C, Stevenaert F et al (2007) KLRG1 binds cadherins and preferentially associates with SHIP-1. Int Immunol 19:391–400

    Article  PubMed  CAS  Google Scholar 

  • Thimme R, Appay V, Koschella M et al (2005) Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. J Virol 79:12112–12116

    Article  PubMed  CAS  Google Scholar 

  • Thomas M, Boname JM, Field S et al (2008) Down-regulation of NKG2D and NKp80 ligands by Kaposi’s sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity. Proc Natl Acad Sci USA 105:1656–1661

    Article  PubMed  CAS  Google Scholar 

  • Vitale M, Bottino C, Sivori S et al (1998) NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells is involved in non-MHC restricted tumor cell lysis. J Exp Med 187:2065–2072

    Article  PubMed  CAS  Google Scholar 

  • Vitale M, Falco M, Castriconi R et al (2001) Identification of NKp80, a novel triggering molecule expressed by human NK cells. Eur J Immunol 31:233–242

    Article  PubMed  CAS  Google Scholar 

  • Voehringer D, Blaser C, Brawand P et al (2001) Viral infections induce abundant numbers of senescent CD8 T cells. J Immunol 167:4838–4843

    PubMed  CAS  Google Scholar 

  • Voehringer D, Koschella M, Pircher H (2002) Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectin like receptor G1 (KLRG1). Blood 100:3698–3702

    Article  PubMed  CAS  Google Scholar 

  • Warren HS, Jones AL, Freeman C, Bettadapura J, Parish CR (2005) Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. J Immunol 175:207–212

    PubMed  CAS  Google Scholar 

  • Welte S, Kuttruff S, Waldhauer I, Steinle A (2006) Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction. Nat Immunol 7:1334–1342

    Article  PubMed  CAS  Google Scholar 

  • Westgaard IH, Dissen E, Torgersen KM et al (2003) The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity. J Expt Med 197:1551–1561

    Article  CAS  Google Scholar 

  • Wilhelm BT, Mager DL (2003) Identification of a new murine lectin-like gene in close proximity to CD94. Immunogenetics 55:53–56

    PubMed  CAS  Google Scholar 

  • Xu R, Abramson J, Fridkin M, Pecht I (2001) SH2 domain-containing inositol polyphosphate 5′-phosphatase is the main mediator of the inhibitory action of the mast cell function-associated antigen. J Immunol 167:6394–6402

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vaccine Production Division, Panacea Biotec, Lalru (Mohali), Punjab, India

    Rajesh K. Gupta (General Manager)

  2. Department of Biophysics, Punjab University, Chandigarh, India

    G. S. Gupta (Former Professor and Chairman)

Authors
  1. Rajesh K. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. S. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Gupta, R.K., Gupta, G.S. (2012). KLRC4, KLRG1, and Natural Cytotoxicity Receptors. In: Animal Lectins: Form, Function and Clinical Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1065-2_32

Download citation

Publish with us

Policies and ethics

Search

Navigation