Skip to main content
SpringerLink
Log in
Book cover

Specificity, Function, and Development of NK Cells pp 41–52Cite as

The CD94/NKG2 C-Type Lectin Receptor Complex

  • Chapter

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 230))

Abstract

NK cell mediated cytotoxicity is suppressed upon specific recognition of target MHC class I molecules (Ljunggren and Kärre 1990). It is currently thought that the control of NK cell activity depends on a subtle balance between inhibitory and activating signals; accordingly, every mature NK cell should bear at least one type of dominant inhibitory receptor for a self MHC class I product, thus preventing autoreactivity against normal cells. Recognition of H-2 products is mediated by members of the Ly-49 C-type lectin family (Yoxoyama 1995). In humans several inhibitory NK cell receptors (NKR) encoded by an immunoglobulin (Ig)-related multigene family specifically interact with different HLA class I allotypes (Colonna and Samaridis 1995; Wagtmann et al. 1995; Lanier and Phillips 1995; Moretra et al. 1996), and the term killer inhibitory receptors (KIRs) has been proposed. A common structural feature of the inhibitory NKR is the presence of cytoplasmic “immunoreceptor tyrosine-based inhibitory motifs” (ITIMs, V/IxYxxL sequences) which upon their tyrosine phosphorylation recruit protein tyrosine phosphatases (SHP-1 and SHP-2) involved in the downregulation of NK cell activity (Burshtyn et al. 1996; Campbell et al. 1996; Fry et al. 1996; Olcese et al. 1996). Remarkably, other members of the Ig superfamily (Ig-SF) NKR trigger NK cell mediated lysis upon their ligation by specific monoclonal antibodies (mAbs). These activating receptors (p50) are closely homologous to inhibitory molecules (p58) but contain shorter intracytoplasmic domains lacking ITIMs and display a different transmembrane region (Moretta et al. 1996).

This is a preview of subscription content, 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   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adamkiewicz TV, McSherry C, Bach FH, Houchins JP (1994) Natural killer lectin-like receptors have divergent carboxy-termini distinct from C-type lectins. Immunogenetics 39: 218

    Article  PubMed  CAS  Google Scholar 

  • Aramburu J, Balboa MA, Ramírez A, Silva A, Acevedo A, Sanchez-Madrid F, de Landâzuri MO, López-Botet M (1990) A novel functional cell surface dimer (Kp43) expressed by natural killer cells and T cell receptor-y/6+ T lymphocytes. Inhibition of IL-2 dependent proliferation by anti-Kp43 monoclonal antibody. J Immunol 144: 3238–3247

    CAS  Google Scholar 

  • Aramburu J, Balboa MA, Izquierdo M, López-Botet M (1991) A novel functional cell surface dimer (Kp43) expressed by natural killer cells and y/S+ T lymphocytes. Modulation of natural killer cytotoxicity by anti Kp43 monoclonal antibody. J Immunol 147: 714–721

    PubMed  CAS  Google Scholar 

  • Aramburu J, Balboa MA, Rodriguez A, Melero I, Alonso M, Alonso JL, López-Botet M (1993) Stimulation of IL-2-activated natural killer cells through the Kp43 surface antigen up-regulates TNF-a production involving the LFA-1 integrin. J Immunol 151: 3420–3429

    PubMed  CAS  Google Scholar 

  • Brooks AG, Posch PE, Scorzelli CJ, Borrego F, Coligan JE (1977) NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor. J Exp Med 185: 795–800

    Article  Google Scholar 

  • Brown MG, Fulmek S, Matsumoto K, Cho R, Lyons PA, Levy ER, Scalzo AA, Yokoyama WM (1977) A 2-Mb YAC contig and physical map of the natural killer gene complex on mouse chromosome 6. Genomics 42: 18–25

    Google Scholar 

  • Brumbaugh KM, Pérez-Villar JJ, Dick CJ, Schoon R, López-Botet M, Leibson PJ (1996) Clonotypic differences in signaling from CD94 (Kp43) on NK cells lead to divergent cellular responses. J Immunol 157: 2804–2812

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Campbell KS, Dessing M, López-Botet M, Cella M, Colonna M (1996) Tyrosine phosphorylation of a human killer inhibitory receptor recruits protein tyrosine phosphatase 1C. J Exp Med 184: 93–100

    Article  PubMed  CAS  Google Scholar 

  • Carretero M, Cantoni C, Bellón T, Bottino C, Biassoni R, Rodriguez A, Pérez-Villar JJ, Moretta L, Moretta A, López-Botet M (1997) The CD94 and NKG2-A C-type lectins covalently assemble to form an NK cell inhibitory receptor for HLA class I molecules. Eur J Immunol

    Google Scholar 

  • Chang C, Rodriguez A, Carretero M, López-Botet M, Phillips J, Lanier LL (1995) Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol 25: 2433–2437

    Article  PubMed  CAS  Google Scholar 

  • Collins TL, Kassner PD, Bierer B, Burakoff SJ (1994) Adhesion receptors in lymphocyte activation. Can Opin Immunol 6: 385–393

    Article  CAS  Google Scholar 

  • Colonna M, Samaridis J (1995) Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition of human Natural Killer cells. Science 268: 405–408

    Article  PubMed  CAS  Google Scholar 

  • Colonna M, Navarro F, Bellón T, Llano M, Garcia P, Samaridis J, Angmann L, Cella M, López-BotetM (1977) A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med 186: 1809–1818

    Google Scholar 

  • Daniels BF, Nakamura MC, Rosen SD, Yokoyama WM, Seaman WE (1995) Ly-49A, a receptor for H-2Dd, has a functional carbohydrate recognition domain. Immunity 1: 785–792

    Article  Google Scholar 

  • Döhring C, Colonna M (1996) Human natural killer cell inhibitory receptors bind to HLA class I molecules. Eur J Immunol 26: 365–369

    Article  PubMed  Google Scholar 

  • Düchler M, Offterdinger M, Holzmüller H, Lipp J, Chu C-T, Aschauer B, Bach FH, Hofer E (1995) NKG2-C is a receptor on human natural killer cells that recognizes structures on K562 target cells. Eur J Immunol 25: 2923–2931

    Article  PubMed  Google Scholar 

  • Fry A, Lanier LL, Weiss A (1996) Phosphotyrosines in the KIR motif of NKB1 are required for negative signaling and for association with PTP1C. J Exp Med 184: 295–300

    Article  PubMed  CAS  Google Scholar 

  • Gudelj L, Deniz G, Rukavina D, Johnson PM, Christmas SE (1996) Expression of functional molecules by human CD3-decidual granular leucocyte clones. Immunology 87: 609–615

    Article  PubMed  CAS  Google Scholar 

  • Gumperz JE, Valiante NM, Parham P, Lanier LL, Tyan D (1996) Heterogeneous phenotypes of expression of the NKB1 natural killer cell class I receptor among individuals of different human histocompatibility leukocyte antigens types appear genetically regulated, but not linked to major histocompatibility complex haplotype. J Exp Med 183: 1817–1827

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Houchins JP, Lanier LL, Niemi EC, Phillips JH, Ryan JC (1977) Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J Immunol 158: 3603–3609

    Google Scholar 

  • Lanier LL (1977) Natural killer cells: from no receptors to too many. Immunity 6: 371–378

    Article  Google Scholar 

  • Lanier LL, Phillips JH (1995) Inhibitory MHC class I receptors on NK cells and T cells. Immunol Today 17: 86–91

    Article  Google Scholar 

  • Lanier LL, Chang C, Phillips JH (1994) Human NKR-P1A: a disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol 153: 2417–2428

    PubMed  CAS  Google Scholar 

  • Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH (1996) Human Natural Killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol 157: 4741–45

    PubMed  CAS  Google Scholar 

  • Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH (1996) Human Natural Killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol 157: 4741–45

    PubMed  CAS  Google Scholar 

  • Ljunggren H-G, Kärre K (1990) In search of the missing self: MHC molecules and NK cell recognition. Immunol Today 11: 237–244

    Article  PubMed  CAS  Google Scholar 

  • López-Botet M (1995) CD94 cluster report: overview of the characterization of the Kp43 NK-cell-associated surface antigen. In: Schlossman SF et al (eds) Leucocyte typing V. Oxford University Press, Oxford

    Google Scholar 

  • López-Botet M, Moretta L, Strominger JL (1996) NK cell-receptors and recognition of MHC class-I molecules. Immunol Today 17: 212–214

    Article  PubMed  Google Scholar 

  • López-Botet M, Moretta L, Strominger JL (1996) NK cell-receptors and recognition of MHC class-I molecules. Immunol Today 17: 212–214

    Article  PubMed  Google Scholar 

  • Moretta A, Vitale M, Sivori S, Bottino C, Morelli L, Augugliaro R, Barbaresi M, Pende D, Ciccone E, López-Botet M, Moretta L (1994) Human natural killer cell receptors for HLA-class I molecules: evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles. J Exp Med 180: 545–555

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC, Moretta L (1996) Receptors for HLA class I molecules in human natural killer cells. Annu Rev Immunol 14: 619–648

    Article  PubMed  CAS  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 PTP1-C and PTP1-D protein tyrosine phosphatases. J Immunol 156: 4531–4534

    PubMed  CAS  Google Scholar 

  • Pazmany L, Mandelboim O, Valés-Gomez M, Davis DM, Reyburn HT, and Strominger JL (1996) Protection from natural killer cell-mediated lysis by HLA-G expression on target cells. Science 274: 792–794

    Article  PubMed  CAS  Google Scholar 

  • Pende D, Sivori S, Accame L, Pareti L, Falco M, Geraghty DE, Le Bouteiller P, Moretta L, Moretta A (1997) HLA-G recognition by human natural killer cells. Involvement of CD94 both as inhibitory and activating receptor complex. Eur J Immunol 27: 1875–1880

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Villar JJ, Melero I, Rodriguez A, Carretero M, Aramburu J, Sivori S, Orengo AM, Moretta A, López-Botet M (1995) Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen. J Immunol 154: 5779–5788

    PubMed  Google Scholar 

  • Pérez-Villar JJ, Carretero M, Navarro F, Melero I, Rodriguez A, Bottino C, Moretta A, López-Botet M (1996) Biochemical and serologic evidence for the existence of functionally distinct forms of the CD94 NK cell receptor. J Immunol 157: 5367–5374

    PubMed  Google Scholar 

  • Pérez-Villar JJ, Melero I, Navarro F, Carretero M, Bellón T, Llano M, Colonna M, Geraghty DE, López-Botet M (1997) The CD94/NKG2-A inhibitory receptor complex is involved in natural killer cell-mediated recognition of cells expressing HLA-Gl. J Immunol 158: 5736–5743

    PubMed  Google Scholar 

  • Phillips JH, Chang C, Mattson J, Gumperz JE, Parham P, Lanier LL (1996) CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, -B, and -C allotypes. Immunity 5: 163–172

    Article  PubMed  CAS  Google Scholar 

  • Renedo M, Arce I, Rodriguez A, Carretero M, Lanier LL, López-Botet M, Fernandez-Ruiz E (1997) The human natural killer gene complex is located on chromosome 12p12-p13. Immunogenetics 46: 307–311

    Article  PubMed  CAS  Google Scholar 

  • Reyburn HT, Mandelboim O, Vales-Gómez M, Davis DM, Pazmany L, Strominger JL (1997) The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells. Nature 386: 514–517

    Article  PubMed  CAS  Google Scholar 

  • Reyburn HT, Mandelboim O, Vales-Gómez M, Davis DM, Pazmany L, Strominger JL (1997) The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells. Nature 386: 514–517

    Article  PubMed  CAS  Google Scholar 

  • Rubio G, Aramburu J, Ontafión J, López-Botet M, Aparicio P (1993) A novel functional cell surface dimer (Kp43) serves as accessory molecule for the activation of a subset of human y/S+ T cells. J Immunol 151: 1312–1321

    PubMed  CAS  Google Scholar 

  • Sivori S, Vitale M, Bottino C, Marcenato E, Sanseverino L, Parolini S, Moretta L, Moretta A (1996) CD94 functions as a natural killer cell inhibitory receptor for different HLA class I alelles: identification of the inhibitory form of CD94 by the use of novel monoclonal antibodies. Eur J Immunol 26: 2487–2492

    Article  PubMed  CAS  Google Scholar 

  • Soderström K, Corliss B, Lanier LL, Phillips JH (1997) CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells. J Immunol 159: 1072–1075

    PubMed  Google Scholar 

  • Thomas ML (1995) Of ITAMs and ITIMs. Turning on and off the B cell antigen receptor. J Exp Med 181: 1953–1956

    Article  PubMed  CAS  Google Scholar 

  • Wagtmann N, Rajagopalan S, Winter CC, Peruzzi M, Long EO (1995) Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. Immunity 3: 801–809

    Article  PubMed  CAS  Google Scholar 

  • Yabe T, McSherry C, Bach FH, Fisch P, Schall RP, Sondel PM, Houchins JP (1993) A multigene family on human chromosome 12 encodes natural killer cell-lectins. Immunogenetics 37: 455–460

    Article  PubMed  CAS  Google Scholar 

  • Yokoyama WM (1995) Natural killer cell receptors. Curr Opin Immunol 7: 110–120

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Diego de León 62, 28006, Madrid, Spain

    M. López-Botet, M. Carretero, T. Bellón, J. J. Pérez-Villar, M. Llano & F. Navarro

Authors
  1. M. López-Botet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Carretero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Bellón
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. J. Pérez-Villar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Llano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Karolinska Institute, Microbiology and Tumor Biology Center, S-17177, Stockholm, Sweden

    Klas Kärre

  2. Basel Institute for Immunology, Grenzacherstraße 487, CH-4005, Basel, Switzerland

    Marco Colonna M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

López-Botet, M., Carretero, M., Bellón, T., Pérez-Villar, J.J., Llano, M., Navarro, F. (1998). The CD94/NKG2 C-Type Lectin Receptor Complex. In: Kärre, K., Colonna, M. (eds) Specificity, Function, and Development of NK Cells. Current Topics in Microbiology and Immunology, vol 230. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46859-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-46859-9_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-46861-2

  • Online ISBN: 978-3-642-46859-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation