SpringerLink
Log in

Activating and Inhibitory NK Cell Receptors

  • Chapter
Mechanisms of Lymphocyte Activation and Immune Regulation VII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 452))

Abstract

Kärre and colleagues observed that tumors lacking H-2 molecules were more susceptible to NK cell-mediated lysis than tumors expressing class I and proposed a unique mechanism of immune surveillance for ‘missing self’ (1). The molecular mechanism responsible for this phenomenon has been defined by the identification of membrane receptors on NK cells that bind to MHC class I on potential target cells. While the NK cell receptors initiating a cell-mediated response against tumors or virus-infected cells are not yet understood, killing of certain target cells can be partially or totally inhibited if the cells express MHC class I molecules that engage inhibitory receptors on the NK cell. Surprisingly, four distinct types of NK cell receptors for MHC class I that inhibit NK cell-mediated cytotoxicity have been identified.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

eBook
EUR 9.99
Price includes VAT (Germany)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
EUR 53.49
Price includes VAT (Germany)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Karre K, Ljunggren HG, Piontek G, Kiessling R: Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defense strategy. Nature 319:675–678, 1986.

    Article  PubMed  CAS  Google Scholar 

  2. Brown MG, Scalzo AA, Matsumoto K, Yokoyama WM: The natural killer gene complex: a genetic basis for understanding natural killer cell function and innate immunity. Immunol. Rev. 155:53–65, 1997.

    Article  PubMed  CAS  Google Scholar 

  3. Kane KP: Ly-49 mediates EL4 lymphoma adhesion to isolated class I major histocompatibility complex molecules. J. Exp. Med. 179:1011–1015, 1994.

    Article  PubMed  CAS  Google Scholar 

  4. Daniels B, Karlhofer FM, Seaman WE, Yokoyama WM: A natural killer cell receptor specific for a major histocompatibility complex class I molecule. J. Exp. Med. 180:687–692, 1994.

    Article  PubMed  CAS  Google Scholar 

  5. Brennan J, Mahon G, Mager DL, Jefferies WA, Takei F: Recognition of class I major histocompatibility complex molecules by Ly-49: Specificities and domain interactions. J. Exp. Med. 183:1553–1559, 1996.

    Article  PubMed  CAS  Google Scholar 

  6. Chang CS, Shen LJ, Gong DE, Kane KP: Major histocompatibility complex class I-dependent cell binding to isolated Ly-49A: Evidence for high-avidity interaction. Eur J Immunol 26:3219–3223, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Matsumoto N, Ribaudo RK, Abastado J-P, Marguiles DH, Yokoyama WM: The lectin-like NK cell receptor Ly-49A recognizes a carbohydrate-independent epitope on its MHC class I ligand. Immunity 8:245–254, 1998.

    Article  PubMed  CAS  Google Scholar 

  8. Daniels BF, Nakamura MC, Rosen SD, Yokoyama WM, Seaman WE: Ly-49A, a receptor for H-2Dd, has a functional carbohydrate recognition domain. Immunity 1:785–792, 1994.

    Article  PubMed  CAS  Google Scholar 

  9. Brennan J, Takei F, Wong S, Mager DL: Carbohydrate recognition by a natural killer cell receptor, Ly-49C. J. Biol. Chem. 270:9691–9694, 1995.

    Article  PubMed  CAS  Google Scholar 

  10. Orihuela M, Margulies DH, Yokoyama WM: The NK cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its MHC class I ligand. Proc. Natl. Acad. Sci. USA 93:11792–11797, 1996.

    Article  PubMed  CAS  Google Scholar 

  11. Correa I, Raulet DH: Binding of diverse peptides to MHC class I molecules inhibits target cell lysis by activated natural killer cells. Immunity 2:61–71, 1995.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Houchins JP, Yabe T, McSherry C, Bach FH: 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, 1991.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Vance RE, Tanamachi DM, Hanke T, Raulet DH: Cloning of a mouse homolog of CD94 extends the family of C-type lectins on murine natural killer cells. Eur. J. Immunol. 27:3236–3241, 1997.

    Article  PubMed  CAS  Google Scholar 

  16. Berg SF, Dissen E, Westgaard IH, Fossum S: Two genes in the rat homologous to human NKG2. Eur. J. Immunol. 28:1998.

    Google Scholar 

  17. Braud VM, Allan DSJ, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, et al.: HLA-E binds to natural killer cell receptors CD94/NKG2A, B, and C. Nature 391:795–798, 1998.

    Article  PubMed  CAS  Google Scholar 

  18. Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG: Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J. Exp. Med. 187:813–818, 1998.

    Article  PubMed  CAS  Google Scholar 

  19. Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, Geraghty DE: HLA-E is a major li-gand for the NK inhibitory receptor CD94/NKG2A. Proc. Natl. Acad. Sci. USA In press, 1998.

    Google Scholar 

  20. Braud V, Jones EY, McMichael A: The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9. Eur J Immunol 27:1164–1169, 1997.

    Article  PubMed  CAS  Google Scholar 

  21. Braud VM, Allan DSJ, Wilson D, McMichael AJ: TAP-and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Current Biology 8:1–10, 1998.

    Article  PubMed  CAS  Google Scholar 

  22. Lee N, Goodlett DR, Ishitani A, Marquardt H, Geraghty DE: HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J. Immunol. In press, 1998.

    Google Scholar 

  23. Aldrich CJ, DeCloux A, Woods AS, Cotter RJ, Soloski MJ, Forman J: Identification of a TAP-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen. Cell 79:649–658, 1994.

    Article  PubMed  CAS  Google Scholar 

  24. Colonna M, Samaridis J: Cloning of Ig-superfamily members associated with HLA-C and HLA-B recognition by human NK cells. Science 268:405–408, 1995.

    Article  PubMed  CAS  Google Scholar 

  25. Wagtmann N, Biassoni R, Cantoni C, Verdiani S, Malnati MS, Vitale M, Bottino C, et al.: Molecular clones of the p58 natural killer cell receptor reveal Ig-related molecules with diversity in both the extra-and intracellular domains. Immunity 2:439–449, 1995.

    Article  PubMed  CAS  Google Scholar 

  26. D’Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH, Lanier LL: Molecular cloning of NKB1: A natural killer cell receptor for HLA-B allotypes. J. Immunol. 155:2306–2310, 1995.

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  29. Fan QR, Garboczi DN, Winter CC, Wagtmann N, Long EO, Wiley DC: Direct binding of a soluble natural killer cell inhibitory receptor to a soluble human leukocyte antigen-Cw4 class I major histocompatibility complex molecule. Proc. Natl. Acad. Sci. USA 93:7178–7183, 1996.

    Article  PubMed  CAS  Google Scholar 

  30. Rojo S, Wagtmann N, Long EO: Binding of a soluble p70 killer cell inhibitory receptor to HLA-B*5101: requirement for all three p70 immunoglobulin domains. Eur. J. Immunol. 27:568–571, 1997.

    Article  PubMed  CAS  Google Scholar 

  31. Winter CC, Long EO: A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes. J. Immunol. 158:4026–4028, 1997.

    PubMed  CAS  Google Scholar 

  32. Rajagopalan S, Long EO: The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide specificity. J. Exp. Med. 185:1523–1528, 1997.

    Article  PubMed  CAS  Google Scholar 

  33. Peruzzi M, Parker KC, Long EO, Malnati MS: Peptide sequence requirements for the recognition of HLA-B*2705 by specific natural killer cells. J. Immunol. 157:3350–3356, 1996.

    PubMed  CAS  Google Scholar 

  34. Valiante NM, Lienert K, Shilling HG, Smits BJ, Parham P: Killer cell receptors: kee** pace with MHC class I evolution. Immunol. Rev. 155:155–164, 1997.

    Article  PubMed  CAS  Google Scholar 

  35. Samaridis J, Colonna M: Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways. Eur. J. Immunol. 27:660–665, 1997.

    Article  PubMed  CAS  Google Scholar 

  36. Colonna M, Navarro F, Bellon T, Llano M, Garcia P, Samaridis J, Angman L, et al.: A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J. Exp. Med. 186:1809–1818, 1997.

    Article  PubMed  CAS  Google Scholar 

  37. Cosman D, Fanger N, Borges L, Kibin M, Chin W, Peterson L, Hus M-L: A novel immunoglobulin super-family receptor for cellular and viral MHC class I molecules. Immunity 7:273–282, 1997.

    Article  PubMed  CAS  Google Scholar 

  38. Thomas ML: Of ITAMS and ITIMs: Turning on and off the B cell antigen receptor. J. Exp. Med. 181:1953–1956, 1995.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. Olcese L, Lang P, Vely F, Cambiaggi A, Marguet D, Blery M, Hippen KL, et al.: Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. J. Immunol. 156:4531–4534, 1996.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  43. Binstadt BA, Brumbaugh KM, Dick CJ, Scharenberg AM, Williams BL, Colonna M, Lanier LL, et al.: Sequential Involvement of Lck and SHP-1 with MHC-Recognizing Receptors on NK Cells Inhibits FcR-Initi-ated Tyrosine Kinase Activation. Immunity 5:629–638, 1996.

    Article  PubMed  CAS  Google Scholar 

  44. Valiante NM, Phillips JH, Lanier LL, Parham P: Killer cell inhibitory receptor recognition of human leukocyte antigen (HLA) class I blocks formation of a pp36/PLC-g signaling complex in human natural killer (NK) cells. J. Exp. Med. 184:2243–2250, 1996.

    Article  PubMed  CAS  Google Scholar 

  45. Vely F, Olivero S, Olcese L, Moretta A, Damen JE, Liu L, Krystal G, et al.: Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs. Eur. J. Immunol. 27:1994–2000, 1997.

    Article  PubMed  CAS  Google Scholar 

  46. Le Drean E, Vely F, Olcese L, Cambiaggi A, Guia S, Krystal G, Gervois N, et al.: Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatase. Eur. J. Immunol. 28:264–276, 1998.

    Article  PubMed  Google Scholar 

  47. Vaage JT, Dissen E, Ager A, Fossum S, Rolstad B: Allospecific recognition of hemic cells in vitro by natural killer cells from athymic rats: evidence that allodeterminants coded for by single major histocompatibility complex haplotypes are recognized. Eur. J. Immunol. 21:2167–2175, 1991.

    Article  PubMed  CAS  Google Scholar 

  48. Rolstad B, Fossum S: Allogeneic lymphocyte cytotoxicity (ALC) in rats: establishment of an in vitro assay, and direct evidence that cells with natural killer (NK) activity are involved in ALC. Immunology 60:151–157, 1987.

    PubMed  CAS  Google Scholar 

  49. Rolstad B, Fossum S: Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats: Spontaneous rejection of allogeneic lymphoid cell grafts by natural killer (NK) cells. Anat. Embryol. 181:215–226,1990.

    Article  PubMed  CAS  Google Scholar 

  50. Mason LH, Anderson SK, Yokoyama WM, Smith HRC, Winkler-Pickett R, Ortaldo JR: The Ly-49D receptor activates murine natural killer cells. J. Exp. Med. 184:2119–2128, 1996.

    Article  PubMed  CAS  Google Scholar 

  51. Biassoni R, Cantoni C, Falco M, Verdiani S, Bottino C, Vitale M, Conte R, et al.: The human leukocyte antigen (HLA)-C-specific “activatory” or “inhibitory” natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions. J. Exp. Med. 183:645–650, 1996.

    Article  PubMed  CAS  Google Scholar 

  52. Moretta L, Sivori S, Vitale M, Pende D, Morelli L, Augugliaro R, Bottino C, et al.: Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. J. Exp. Med. 182:875–884, 1995.

    Article  PubMed  CAS  Google Scholar 

  53. Houchins JP, Lanier LL, Niemi E, Phillips JH, Ryan JC: Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J. Immunol. 158:3603–3609, 1997.

    PubMed  CAS  Google Scholar 

  54. Mason LH, Willette-Brown J, Anderson SK, Gosselin P, Shores EW, Love PE, Ortaldo JR, et al.: Characterization of an associated 16 kDA tyrosine phosphoprotein required for Ly-49D signal transduction. J. Immunol. In press, 1998.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Valiante NM, Uhrberg M, Shilling HG, Lienert-Weidenbach K, Arnett KL, D’Andrea A, Phillips JH, et al.: Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 7:739–751, 1997.

    Article  PubMed  CAS  Google Scholar 

  57. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, et al.: Human diversity in killer cell inhibitory receptor (KIR) genes. Immunity 7:753–763, 1997.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunobiology, DNAX Research Institute, 901 California Avenue, Palo Alto, California, 94304, USA

    Lewis L. Lanier

Authors
  1. Lewis L. Lanier
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California, Irvine, Irvine, California, USA

    Sudhir Gupta

  2. National Institutes of Health, Bethesda, Maryland, USA

    Alan Sher

  3. Emory University, Atlanta, Georgia, USA

    Rafi Ahmed

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lanier, L.L. (1998). Activating and Inhibitory NK Cell Receptors. In: Gupta, S., Sher, A., Ahmed, R. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VII. Advances in Experimental Medicine and Biology, vol 452. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5355-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5355-7_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7443-5

  • Online ISBN: 978-1-4615-5355-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation