Skip to main content
Log in

Molecular cloning of KLRI1 and KLRI2, a novel pair of lectin-like natural killer-cell receptors with opposing signalling motifs

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

We here report the molecular cloning of a novel family of killer-cell lectin-like (KLR) receptors in the rat and the mouse, termed KLRI. In both species, there are two members, KLRI1 and KLRI2. While the extracellular lectin-like domains of KLRI1 and KLRI2 are similar [74% (rat) and 83% (mouse) amino acid identity], they differ intracellularly. KLRI1 has two immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic domain, suggesting an inhibitory function. KLRI2 has no ITIM, but a positively charged lysine residue in the transmembrane region, suggesting association with activating adapter molecules. Klri1 and Klri2 are localized within the natural killer (NK) cell gene complex on rat chromosome 4 and mouse chromosome 6. By RT-PCR and Northern blot analysis KLRI1 and KLRI2 were selectively expressed by NK cells in both rat and mouse. Epitope-tagged expression constructs of rat KLRI1 and rat KLRI2 induced surface expression of a nondisulphide-linked protein of Mr 36,000/39,000 and Mr 34,000, respectively.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    CAS  PubMed  Google Scholar 

  • Arase N, Arase H, Park SY, Ohno H, Ra C, Saito T (1997) Association with FcRγ is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells. J Exp Med 186:1957–1963

    Article  Google Scholar 

  • Berg SF, Dissen E, Westgaard IH, Fossum S (1998) Two genes in the rat homologous to human NKG2. Eur J Immunol 28:444–450

    Article  Google Scholar 

  • Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220

    Article  CAS  PubMed  Google Scholar 

  • Brown MG, Fulmek S, Matsumoto K, Cho R, Lyons PA, Levy ER, Scalzo AA, Yokoyama WM (1997) A 2-Mb YAC contig and physical map of the natural killer gene complex on mouse chromosome 6. Genomics 42:16–25

    Article  CAS  PubMed  Google Scholar 

  • Bruhns P, Marchetti P, Fridman WH, Vivier E, Daeron M (1999) Differential roles of N- and C-terminal immunoreceptor tyrosine-based inhibition motifs during inhibition of cell activation by killer cell inhibitory receptors. J Immunol 162:3168–3175

    Google Scholar 

  • Burshtyn DN, Scharenberg AM, Wagtmann N, Rajagopalan S, Berrada K, Yi T, Kinet JP, Long EO (1996) Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor. Immunity 4:77–85

    Article  Google Scholar 

  • Burshtyn DN, Lam AS, Weston M, Gupta N, Warmerdam PA, Long EO (1999) Conserved residues amino-terminal of cytoplasmic tyrosines contribute to the SHP-1-mediated inhibitory function of killer cell Ig-like receptors. J Immunol 162:897–902

    Google Scholar 

  • Diefenbach A, Tomasello E, Lucas M, Jamieson AM, Hsia JK, Vivier E, Raulet DH (2002) Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol 3:1142–1149

    Article  CAS  PubMed  Google Scholar 

  • Dissen E, Berg SF, Westgaard IH, Fossum S (1997) Molecular characterization of a gene in the rat homologous to human CD94. Eur J Immunol 27:2080–2086

    CAS  PubMed  Google Scholar 

  • Dissen E, Ryan JC, Seaman WE, Fossum S (1996) An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes. J Exp Med 183:2197–2207

    Article  CAS  PubMed  Google Scholar 

  • Granucci F, Girolomoni G, Lutz MB, Foti M, Marconi G, Gnocchi P, Nolli L, Ricciardi-Castagnoli P (1994) Modulation of cytokine expression in mouse dendritic cell clones. Eur J Immunol 24:2522–2526

    Google Scholar 

  • Houchins JP, Yabe T, McSherry C, Bach FH (1991) DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J Exp Med 173:1017–1020

    Article  CAS  PubMed  Google Scholar 

  • Koren HS, Handwerger BS, Wunderlich JR (1975) Identification of macrophage-like characteristics in a cultured murine tumor line. J Immunol 114:894–897

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Lanier LL (2003) Natural killer cell receptor signaling. Curr Opin Immunol 15:308–314

    Google Scholar 

  • Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH (1998b) Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 391:703–707

    Article  CAS  PubMed  Google Scholar 

  • Lanier LL, Corliss B, Wu J, Phillips JH (1998c) Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 8:693–701

    Article  Google Scholar 

  • Lanier LL, Yu G, Phillips JH (1991) Analysis of FcγRIII (CD16) membrane expression and association with CD3ζ and FcεRIγ by site-directed mutation. J Immunol 146:1571–1576

    Google Scholar 

  • Lohwasser S, Hande P, Mager DL, Takei F (1999) Cloning of murine NKG2A, B and C: second family of C-type lectin receptors on murine NK cells. Eur J Immunol 29:755–761

    Article  Google Scholar 

  • Long EO (1999) Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875–904

    Article  Google Scholar 

  • Løvik G, Vaage JT, Dissen E, Szpirer C, Ryan JC, Rolstad B (2000) Characterization and molecular cloning of rat C1qRp, a receptor on NK cells. Eur J Immunol 30:3355–3362

    Article  Google Scholar 

  • Matloubian M, David A, Engel S, Ryan JC, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304

    Article  Google Scholar 

  • Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A (2002) Human natural killer cells: their origin, receptors and function. Eur J Immunol 32:1205–1211

    Article  Google Scholar 

  • Nakamura MC, Niemi EC, Fisher MJ, Shultz LD, Seaman WE, Ryan JC (1997) Mouse Ly-49A interrupts early signaling events in natural killer cell cytotoxicity and functionally associates with the SHP-1 tyrosine phosphatase. J Exp Med 185:673–684

    Article  Google Scholar 

  • Naper C, Hayashi S, Løvik G, Kveberg L, Niemi EC, Rolstad B, Dissen E, Ryan JC, Vaage JT (2002) Characterization of a novel killer cell lectin-like receptor (KLRH1) expressed by alloreactive rat NK cells. J Immunol 168:5147–5154

    CAS  PubMed  Google Scholar 

  • Olcese L, Lang P, Vely F, Cambiaggi A, Marguet D, Blery M, Hippen KL, Biassoni R, Moretta A, Moretta L, Cambier JC, Vivier E (1996) Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. J Immunol 156:4531–4534

    Google Scholar 

  • Page RD (1996) TreeView: an application to display phylogenetic trees on personal computers. Comput Appl Biosci 12:357–358

    CAS  PubMed  Google Scholar 

  • Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R, Morelli L, Marcenaro E, Accame L, Malaspina A, Biassoni R, Bottino C, Moretta L, Moretta A (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  Google Scholar 

  • Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, Biassoni R, Moretta A (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  Google Scholar 

  • Rolstad B, Naper C, Løvik G, Vaage JT, Ryan JC, Backman-Petersson E, Kirsch RD, Butcher GW (2001) Rat natural killer cell receptor systems and recognition of MHC class I molecules. Immunol Rev 181:149–157

    Article  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882

    Article  CAS  PubMed  Google Scholar 

  • Tormo J, Natarajan K, Margulies DH, Mariuzza RA (1999) Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature 402:623–631

    Article  Google Scholar 

  • Vely F, Olivero S, Olcese L, Moretta A, Damen JE, Liu L, Krystal G, Cambier JC, Daeron M, Vivier E (1997) Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs. Eur J Immunol 27:1994–2000

    Google Scholar 

  • Weis WI, Taylor ME, Drickamer K (1998) The C-type lectin superfamily in the immune system. Immunol Rev 163:19–34

    CAS  PubMed  Google Scholar 

  • Westgaard IH, Dissen E, Torgersen KM, Lazetic S, Lanier LL, Phillips JH, Fossum S (2003) The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity. J Exp Med 197:1551–1561

    Article  Google Scholar 

  • Wolan DW, Teyton L, Rudolph MG, Villmow B, Bauer S, Busch DH, Wilson IA (2001) Crystal structure of the murine NK cell-activating receptor NKG2D at 1.95 A. Nat Immunol 2:248–254

    Article  Google Scholar 

  • Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH (1999) An activating immunoreceptor complex formed by NKG2D and DAP10. Science 285:730–732

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama WM, Plougastel BFM (2003) Immune functions encoded by the natural killer gene complex. Nat Rev Immunol 3:304–316

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama WM, Ryan JC, Hunter JJ, Smith HR, Stark M, Seaman WE (1991) cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6. J Immunol 147:3229–3236

    Google Scholar 

Download references

Acknowledgements

We thank M. Lauritzen and W. Jensen for technical assistance and L.L. Spruyt and J.G.M.C. Damoiseaux for sharing reagents. This work was supported by the Norwegian Research Council, the Norwegian Cancer Society, and Bergljot and Sigurd Skaugen’s Fund. J.C. Ryan was supported by National Institutes of Health RO1 AI 44126 and by the US Veterans Administration.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Per C. Saether.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saether, P.C., Westgaard, I.H., Flornes, L.M. et al. Molecular cloning of KLRI1 and KLRI2, a novel pair of lectin-like natural killer-cell receptors with opposing signalling motifs. Immunogenetics 56, 833–839 (2005). https://doi.org/10.1007/s00251-004-0759-x

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-004-0759-x

Keywords

Navigation