Natural Killer Cell Receptors

  • Roberto Biassoni
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 640)

Abstract

Natural killer (NK) cells are an important arm of the innate immune response that are directly involved in the recognition and lysis of virus-infected and tumor cells. Such function is under the control of a complex array of germline-encoded receptors able to deliver either inhibitory or activating signals. The majority of inhibitory receptors expressed by NK cells are major histocompatibility complex (MHC) class I-specific and display clonal and stochastic distribution on the cell surface. Thus, a given NK cell expresses at least one self class I inhibitory receptor. Under normal conditions, the strength of inhibitory signals delivered by multiple interactions always overrides the activating signals, resulting in NK cell self-tolerance. Under certain pathological conditions, such as viral infections or tumor transformation, the delicate balance of inhibition versus activation is broken, resulting in downregulation or loss of MHC class I expression. In general, the degree of inhibition induced by class I-specific receptors is proportional to the amount of these molecules on the cell surface. Thus, in transformed cells, this inhibition can be overridden by the triggering signal cascades, leading to cell activation. The majority of triggering receptors expressed by NK cells belong to the multichain immune recognition receptor (MIRR) family and use separate signal-transducing Polypeptides similar to those used by other immune receptors such as the T-cell antigen receptor, the B-cell antigen receptor and other receptors expressed by myeloid cells. Inhibitory receptors are not members of the MIRR family but they are relevant for a better understanding the exquisite equilibrium and regulatory crosstalk between positive and negative signals.

Keywords

Natural Killer Cell Major Histocompatibility Complex Class Human Leukocyte Antigen Class Human Natural Killer Cell NKG2D Ligand 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Ljunggren H-G, Karre K. In search of the missing self. MHC molecules and NK cell recognition. Im-munol Today 1990; 11:237–44.CrossRefGoogle Scholar
  2. 2.
    Biassoni R, Dimasi N. Human Natural Killer cell receptor functions and their implication in diseases. Expert Rev Clin Immunol 2005; 1:405–17.CrossRefGoogle Scholar
  3. 3.
    Moretta A, Bottino C, Vitale M et al. Receptors for HLA class I molecules in human natural killer cells. Annu Rev Immunol 1996; 14:619–48.PubMedCrossRefGoogle Scholar
  4. 4.
    Moretta A, Bottino C, Vitale M et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 2001; 19:197–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Sigalov AB. Multichain immune recognition receptor signaling: Different players, same game? Trends Immunol 2004; 25:583–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Dimasi N, Biassoni R. Structural and functional aspects of the Ly49 natural killer cell receptors. Im-munol Cell Biol 2005; 83:1–8.CrossRefGoogle Scholar
  7. 7.
    Lopez-Botet M, Llano M, Navarro F et al. NK cell recognition of nonclassical HLA class I molecules. Semin Immunol 2000; 12:109–19.PubMedCrossRefGoogle Scholar
  8. 8.
    Long EO. Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 1999; 17:875–04.PubMedCrossRefGoogle Scholar
  9. 9.
    Vitale M, Delia Chiesa M, Carlomagno S et al. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood 2005; 106:566–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferlazzo G, Tsang ML, Moretta L et al. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 2002; 195:343–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Moretta A. The dialogue between human natural killer cells and dendritic cells. Curr Opin Immunol 2005; 17:306–11.PubMedCrossRefGoogle Scholar
  12. 12.
    Kelley J, Walter L, Trowsdale J. Comparative genomics of natural killer cell receptor gene clusters. PLoS Genet 2005; 1:129–39.PubMedCrossRefGoogle Scholar
  13. 13.
    Cosman D, Fänger N, Borges L et al. A novel Immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity 1997; 7:273–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Vitale M, Castriconi R, Parolini S et al. The leukocyte Ig-like receptor (LIR)-l for the cytomegalovirus ULI8 protein displays a broad specificity for different HLA class I alleles: analysis of LIR-1 + NK cell clones. Int Immunol 1999; 11:29–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Vance RE, Kraft JR, Altman JD et al. Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-l(b). J Exp Med 1998; 188:1841–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaiser BK, Barahmand-Pour F, Paulsene W et al. Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics. J Immunol 2005; 174:2878–84.PubMedGoogle Scholar
  17. 17.
    Llano M, Lee N, Navarro F et al. HLA-E-bound peptides influence recognition by inhibitory and trig-gering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol 1998; 28:2854–63.PubMedCrossRefGoogle Scholar
  18. 18.
    Brooks CR, Elliott ?, Parham P et al. The inhibitory receptor NKG2A determines lysis of vaccinia virus-infected autologous targets by NK cells. J Immunol 2006; 176:1141–7.PubMedGoogle Scholar
  19. 19.
    Ciccone E, Pende D, Viale O et al. Involvement of HLA class I alleles in NK cell specific functions: Expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2). J Exp Med 1992; 176:963–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Colonna M, Borsellino G, Falco M et al. HLA-is the inhibitory ligand that determines dominant resistance to lysis by NK1-and NK2-specific natural killer cells. Proc Natl Acad Sci USA 1993; 90:12000–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Biassoni R, Falco M, Cambiaggi A et al. Amino acid substitutions can influence the NK-mediated recognition of HLA-C molecules. Role of Serine-77 and lysine-80 in the target cell protection from lysis mediated by group 2 or group 1 NK clones. J Exp Med 1995; 182:605–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Moretta A, Biassoni R, Bottino C et al. Major histocompatibility complex class I-specific receptors on human natural killer and T lymphocytes. Immunol Rev 1997; 155:105–17.PubMedCrossRefGoogle Scholar
  23. 23.
    Malnati MS, Peruzzi M, Parker KC et al. Peptide specificity in the recognition of MHC class I by natural killer cell clones. Science 1995; 267:1016–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Costello PS, Walters AE, Mee PJ et al. The Rho-family GTP exchange factor Vav is a critical transducer of T-cell receptor signals to the calcium, ERK and NF-B pathways. Proc Natl Acad Sci USA 1999; 96:3035–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Penninger JM, Crabtree GR. The actin cytoskeleton and lymphocyte activation. Cell 1999; 96:9–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Kon-Kozlowski M, Pani G, Pawson t et al. The tyrosine phosphatase PTP1C associates withVav, Grb,2 andmSosl in hematopoietic cells. J Biol Chem 1996; 271:3856–62.PubMedCrossRefGoogle Scholar
  27. 27.
    Stebbins CC, Watzl C, Billadeau DD et al. Vavl dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicity. Mol Cell Biol 2003; 23:6291–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279:509–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Billadeau DD, Brumbaugh KM, Dick CJ et al. The Vav-Racl pathway in cytotoxic lymphocytes regulates the generation of cell-mediated killing. J Exp Med 1998; 188:549–59.PubMedCrossRefGoogle Scholar
  30. 30.
    Yokoyama WM, Kim S, French AR. The dynamic life of natural killer cells. Annu Rev Immunol 2004; 22:405–29PubMedCrossRefGoogle Scholar
  31. 31.
    Lanier LL, Corliss BC, Wu J et al. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 1998; 391:703–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Jiang K, Zhong B, Gilvary DL et al. Pivotal role of phosphoinositide-3 kinase in regulation of cyto-toxicity in natural killer cells. Nat Immunol 2000; 1:419–25.PubMedCrossRefGoogle Scholar
  33. 33.
    Chang C, Dietrich J, Harpur AG et al. Cutting edge: 10, a novel transmembrane adapter protein genetically linked to DAP 12 but with unique signaling properties. J Immunol 1999; 163:4651–4.PubMedGoogle Scholar
  34. 34.
    Wu J, Song Y, Bakker ABH et al. An activating receptor complex on natural killer and ? cells formed by NKG2D and DAP10. Science 1999; 285:730–2.PubMedCrossRefGoogle Scholar
  35. 35.
    Moretta A, Biassoni R, Bottino C et al. Natural cytotoxicity receptors that trigger human NK-cell-me-diated cytolysis. Immunol. Today 2000; 21:228–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Augugliaro R, Parolini S, Castriconi R et al. Selective crosstalk among natural cytotoxicity receptors in human natural killer cells. Eur J Immunol 2003; 33:1235–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Biassoni R, Cantoni C, Marras D et al. Human natural killer cell receptors: Insights into their molecular function and structure. J Cell Mol Med 2003; 7:376–87.PubMedCrossRefGoogle Scholar
  38. 38.
    Pessino A, Sivori S, Bottino C et al. Molecular cloning of NKp46: A novel member of the Immuno-globulin superfamily involved in triggering of natural cytotoxicity. J Exp Med 1998; 188:953–60.PubMedCrossRefGoogle Scholar
  39. 39.
    Biassoni R, Pessino A, Bottino C et al. The murine homologue of the human NKp46, a triggering receptor involved in the induction of natural cytotoxicity. Eur J Immunol 1999; 29:1014–20.PubMedCrossRefGoogle Scholar
  40. 40.
    Falco M, Cantoni C, Bottino C et al. Identification of the rat homologue of the human NKp46 trig-gering receptor. Immunol Lett 1999; 68:411–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Westgaard IH, Berg SF, Vaage JT et al. Rat NKp46 activates natural killer cell cytotoxicity and is associated with FcepsilonRIgamma and CD3zeta. J Leukoc Biol 2004; 76:1200–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Storset AK, Kulberg S, Berg I et al. NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics. Eur J Immunol 2004; 34:669–76.PubMedCrossRefGoogle Scholar
  43. 43.
    DeMaria A, Biassoni R, Fogli M et al. Identification, molecular cloning and functional characteriza-tion of NKp46 and NKp30 natural cytotoxicity receptors in Macaca fascicularis (Macaca rhesus) NK cells. Eur J Immunol 2001; 31:3546–56.PubMedCrossRefGoogle Scholar
  44. 44.
    Rutjens E, Mazza S, Biassoni R et al. Differential NKp30 inducibility is associated with conserved NK cell phenotype and function and maintenance of function in AIDS resistant chimpanzees. J Immunol 2007; 178:1702–12.PubMedGoogle Scholar
  45. 45.
    Ponassi M, Cantoni C, Biassoni R et al. Structure of the human NK cell triggering receptor NKp46 ectodomain. Biochem Biophys Res Comm 2003; 309:317–23.PubMedCrossRefGoogle Scholar
  46. 46.
    Foster CE, Colonna M, Sun PD. Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors. J Biol Chem 2003; 278:46081–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Sivori S, Pende D, Bottino C et al. NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells. Eur J Immunol 1999; 29:1656–66.PubMedCrossRefGoogle Scholar
  48. 48.
    Sivori S, Parolini S, Marcenaro E et al. Triggering receptors involved in natural killer cell-mediated cytotoxicity against choriocarcinoma cell lines. Hum Immunol 2000; 61:1055–58.PubMedCrossRefGoogle Scholar
  49. 49.
    Sivori S, Parolini S, Marcenaro E et al. Involvement of natural cytotoxicity receptors in human natural killer cell-mediated lysis of neuroblastoma and glioblastoma cell lines. J Neuroimmunol 2000; 107:220–25.PubMedCrossRefGoogle Scholar
  50. 50.
    Weiss L, Reich S, Mandelboim O at el. Murine B-cell leukemia lymphoma (BCL1) cells as a target for NK cell-mediated immunotherapy. Bone Marrow Transplant 2004; 33:1137–41.PubMedCrossRefGoogle Scholar
  51. 51.
    Spaggiari GM, Carosio R, Pende D et al. NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. Eur J Immunol 2001; 31:1656–65.PubMedCrossRefGoogle Scholar
  52. 52.
    Costello RT, Sivori S, Marcenaro M et al. Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood 2002; 99:3661–67.PubMedCrossRefGoogle Scholar
  53. 53.
    Mandelboim O, Lieberman N, Lev M et al. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 2001; 409:1055–60.PubMedCrossRefGoogle Scholar
  54. 54.
    Gazit R, Gruda R, Elboim M et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncrl. Nat Immunol 2006; 7:517–23.PubMedCrossRefGoogle Scholar
  55. 55.
    Garg A, Barnes PF, Porgador A et al. Vimentin expressed on Mycobacterium tubercolosis-infected human monocytes is involved in binding to the NKp46 receptor. J Immunol 2006; 177:6192–8PubMedGoogle Scholar
  56. 56.
    Bloushtain N, Qimron U, Bar-Ilan A et al. Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. J Immunol 2004; 173:2392–401.PubMedGoogle Scholar
  57. 57.
    Warren HS, Jones AL, Freeman C et al. Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. J Immunol 2005; 175:207–12.PubMedGoogle Scholar
  58. 58.
    Arnon TI, Achdout H, Lieberman N et al. The mechanisms controlling the recognition of tumor-and virus-infected cells by NKp46. Blood 2004; 103:664–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Marcenaro E, Augugliaro R, Falco M et al. CD 59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity. Eur J Immunol 2003; 33:3367–76.PubMedCrossRefGoogle Scholar
  60. 60.
    Arnon TI, Achdout H, Levi O et al. Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Nat Immunol 2005; 6:515–23.PubMedCrossRefGoogle Scholar
  61. 61.
    Trowsdale J. Genetic and functional relationships between MHC and NK receptor genes. Immunity 2001; 15(3):363–74.PubMedCrossRefGoogle Scholar
  62. 62.
    Hollyoake M, Campbell RD, Aguado B. NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli. Mol Biol Evol 2005; 22:1661–72.PubMedCrossRefGoogle Scholar
  63. 63.
    Ferlazzo G, Pack M, Thomas D et al. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci USA 2004; 101:16606–11.PubMedCrossRefGoogle Scholar
  64. 64.
    Cantoni C, Bottino C, Vitale M et al. 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 1999; 189:787–96.PubMedCrossRefGoogle Scholar
  65. 65.
    von Lilienfeld-Toal M, Nattermann J, Feldmann G et al. Activated gammadelta T-cells express the natural cytotoxicity receptor natural killer p44 and show cytotoxic activity against myeloma cells. Clin Exp Immunol 2006; 144:528–33.CrossRefGoogle Scholar
  66. 66.
    Cantoni C, Ponassi M, Biassoni R et al. The three-dimensional structure of NK cell receptor NKp44, a triggering partner in natural cytotoxicity. Structure 2003; 11:725 34.PubMedCrossRefGoogle Scholar
  67. 67.
    Campbell KS, Yusa S, Kikuchi-Maki A et al. NKp44 triggers NK cell activation through DAP 12 association that is not influenced by a putative cytoplasmic inhibitory sequence. J Immunol 2004; 172:899–06.PubMedGoogle Scholar
  68. 68.
    Allcock RJ, Barrow AD, Forbes S et al. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Eur J Immunol 2003; 33:567–77.PubMedCrossRefGoogle Scholar
  69. 69.
    May AP, Robinson RC, Vinson M et al. Crystal structure of the N-terminal domain of sialoadhesin in complex with sialyllactose at 1.85 A resolution Mol Cell 1998; 1:719–28.Google Scholar
  70. 70.
    Swaminathan CP, Wais N, Vyas W et al. Entropically assisted carbohydrate recognition by a natural killer cell surface receptor. Chembiochem 2004; 5:1571–75.PubMedCrossRefGoogle Scholar
  71. 71.
    Attrill H, Takazawa H, Witt S et al. The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design. Biochem J 2006; 397:271–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Arnon TI, Lev M, Katz G et al. Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur. J Immunol 2001; 31:2680–89.CrossRefGoogle Scholar
  73. 73.
    Rosen DB, Araki M, Hamerman JA et al. A Structural basis for the association of DAP 12 with mouse, but not human, NKG2D. J Immunol 2004; 173:2470–8.PubMedGoogle Scholar
  74. 74.
    Watzl C. The NKG2D receptor and its ligands-recognition beyond the missing self? Microbes Infect 2003; 5:31–37.PubMedCrossRefGoogle Scholar
  75. 75.
    Sutherland CL, Chalupny NJ, Schooley K et al. UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol 2002; 168:671–9.PubMedGoogle Scholar
  76. 76.
    Diefenbach A, Tomasello E, Lucas M et al. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol 2002; 3:1142–9. Erratum in: Nat Immunol 2004; 5:658.PubMedCrossRefGoogle Scholar
  77. 77.
    Zompi S, Hamerman JA, Ogasawara K et al. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol 2003; 4:565–72.PubMedCrossRefGoogle Scholar
  78. 78.
    Bauer S, Groh V, Wu J et al. Activation of NK cells and T-cells by NKG2D, a receptor for stress-in-ducible MICA. Science 1999; 285:727–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Biassoni R, Fogli M, Cantoni C et al. 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 2005; 174:5695–705.PubMedGoogle Scholar
  80. 80.
    Cosman D, Mullberg J, Sutherland CL et al. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein ULI6 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 2001; 14:123–33.PubMedCrossRefGoogle Scholar
  81. 81.
    Jan Chalupny N, Sutherland CL, Lawrence WA et al. ULBP4 is a novel ligand for human NKG2D. Biochem Biophys Res Commun 2003; 305:129–35.PubMedCrossRefGoogle Scholar
  82. 82.
    Bacon L, Eagle RA, Meyer M et al. Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D. J Immunol 2004; 173:1078–84.PubMedGoogle Scholar
  83. 83.
    Bahram S, Inoko H, Shiina T et al. MIC and other NKG2D ligands: From none to too many. Curr Opin Immunol 2005; 17:505–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Gleimer M, Parham P. Stress management: MHC class I and class I-like molecules as reporters of cellular stress. Immunity 2003; 19(4):469–77.PubMedCrossRefGoogle Scholar
  85. 85.
    Eagle RA, Traherne JA, Ashiru O et al. Regulation of NKG2D ligand gene expression. Hum Immunol 2006; 67:159–69.PubMedCrossRefGoogle Scholar
  86. 86.
    Krmpotic A, Busch DH, Bubic I et al. MCMV glycoprotein gp40 confers virus resistance to CD8+ T-cells and NK cells in vivo. Nat Immunol 2002; 3:529–35.PubMedCrossRefGoogle Scholar
  87. 87.
    Krmpotic A, Hasan M, Loewendorf A et al. NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m 145. J Exp Med 2005;201:211–20.PubMedCrossRefGoogle Scholar
  88. 88.
    Hasan M, Krmpotic A, Ruzsics Z et al. Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m 155 glycoprotein. J Virol 2005; 79:2920–30.PubMedCrossRefGoogle Scholar
  89. 89.
    Chalupny NJ, Rein-Weston A, Dosch S et al. Down-regulation of the NKG2D ligand MICA by the human cytomegalovirus glycoprotein UL142. Biochem Biophys Res Commun 2006; 346:175–81.PubMedCrossRefGoogle Scholar
  90. 90.
    Radaev S, Kattah M, Zou Z et al. Making sense of the diverse ligand recognition by NKG2D. J Im-munol 2002; 169:6279–85.Google Scholar
  91. 91.
    McFarland BJ, Strong RK. Thermodynamic analysis of degenerate recognition by the NKG2D im-munoreceptor: not induced fit but rigid adaptation. Immunity 2003; 19:803–12.PubMedCrossRefGoogle Scholar
  92. 92.
    Biassoni R, Cantoni C, Falco M 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 1996; 183:645–650.PubMedCrossRefGoogle Scholar
  93. 93.
    Abi-Rached L, Parham P. Natural selection drives recurrent formation of activating killer cell immu-noglobulin-like receptor and Ly49 from inhibitory homologues. J Exp Med 2005; 201:1319–32.PubMedCrossRefGoogle Scholar
  94. 94.
    Bottino C, Falco M, Sivori S et al. Identification and molecular characterization of a natural mutant of the p50.2/KIR2DS2 activating NK receptor that fails to mediate NK cell triggering. Eur J Immunol 2000; 30:3569–3574.PubMedCrossRefGoogle Scholar
  95. 95.
    Biassoni R, Pessino A, Malaspina A et al. Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur J Immunol 1997; 27:3095–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Katz G, Markel G, Mizrahi S et al. Recognition of HLA Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail number 4. J Immunol 2001; 166:7260–7.PubMedGoogle Scholar
  97. 97.
    Katz G, Gazit R, Arnon TI et al. MHC class I-independent recognition of NK-activating receptor KIR2DS4. J Immunol 2004; 173:1819–25.PubMedGoogle Scholar
  98. 98.
    Vales-Gomez M, Reyburn HT, Erskine RA et al. Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors. Proc Nat Acad Sci USA 1998; 95:14326–31.PubMedCrossRefGoogle Scholar
  99. 99.
    Maenaka K, Juji T, Nakayama T et al. Killer cell Immunoglobulin receptors and T-cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties. J Biol Chem 1999; 274:28329–34.PubMedCrossRefGoogle Scholar
  100. 100.
    Lanier LL, Corliss B, Wu J et al. Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 1998; 8:693–01.PubMedCrossRefGoogle Scholar
  101. 101.
    Braud VM, Allan DS, O’Callaghan CA et al. HLA-E binds to natural killer cell receptors CD94/ NKG2A, and Nature 1998; 391:795–9.Google Scholar
  102. 102.
    Wada H, Matsumoto N, Maenaka K et al. The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues. Eur J Immunol 2004; 34:81–90.PubMedCrossRefGoogle Scholar
  103. 103.
    Kubin MZ, Parshley DL, Din W et al. Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48. Eur J Immunol 1999; 29:3466–77.PubMedCrossRefGoogle Scholar
  104. 104.
    Parolini S, Bottino C, Falco M et al. X-linked lymphoproliferative disease: 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of NK cells to kill EBV-infected cells. J Exp Med 2000; 192:347–58.CrossRefGoogle Scholar
  105. 105.
    Bottino C, Augugliaro R, Castriconi R et al. Analysis of the molecular mechanism involved in 2B4-mediated NK cell activation: evidence that human 2B4 is physically and functionally associated with the linker for activation of T-cells (LAT). Eur J Immunol 2000; 30:3718–22.PubMedCrossRefGoogle Scholar
  106. 106.
    Eissmann P, Beauchamp L, Wooters J et al. Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244). Blood 2005; 105:4722–9PubMedCrossRefGoogle Scholar
  107. 107.
    Bottino C, Falco M, Parolini S et al. NTB-A, a novel SH2DlA-associated surface molecule contributing to the inability of NK cells to kill EBV-infected-cells in X-linked lymphoproliferative disease. J Exp Med 2001; 194:235–46.PubMedCrossRefGoogle Scholar
  108. 108.
    Flaig RM, Stark S, Watzl C. Cutting edge: NTB-A activates NK cells via homophilic interaction. J Immunol 2004; 172:6524–7.PubMedGoogle Scholar
  109. 109.
    Stark S, Watzl C. 2B4 (CD244), NTB-A and CRACC (CS1) stimulate cytotoxicity but no proliferation in human NK cells. Int Immunol 2006; 18:241–7.PubMedCrossRefGoogle Scholar
  110. 110.
    Vitale M, Falco M, Castriconi R et al. Identification of NKp,80 a novel triggering molecule expressed by human natural killer cells. Eur J Immunol 2001; 31:233–42.PubMedCrossRefGoogle Scholar
  111. 111.
    Weite S, Kuttruff S, Waldhauer I et al. Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction. Nat Immunol 2006; 7:1334–42.CrossRefGoogle Scholar
  112. 112.
    Lanier LL, Chang C, Phillips JH. Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and ? lymphocytes. J Immunol 1994; 153:2417–28.PubMedGoogle Scholar
  113. 113.
    Rosen DB, Bettadapura J, Alsharifi M et al. Cutting edge: Lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol 2005; 175:7796–9.PubMedGoogle Scholar
  114. 114.
    Aldemir H, Prod’homme V, Dumaurier MJ et al. Cutting edge: Lectin-like transcript 1 is a ligand for the CD161 receptor. J Immunol 2005; 175:7791–5.PubMedGoogle Scholar
  115. 115.
    Shibuya A, Campbell D, Hannum C et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of ? lymphocytes. Immunity 1996; 4:573–81.PubMedCrossRefGoogle Scholar
  116. 116.
    Bottino C, Castriconi R, Pende D et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med 2003; 198:557–67.PubMedCrossRefGoogle Scholar
  117. 117.
    Tahara-Hanaoka S, Shibuya K, Onoda Y et al. Functional characterization of DNAM-1 (CD226) inter-action with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). Int Immunol 2004; 16:533–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Markel G, Lieberman N, Katz G et al. CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol 2002; 168:2803–10.PubMedGoogle Scholar
  119. 119.
    Stern N, Markel G, Arnon TI et al. Carcinoembryonic antigen (CEA) inhibits NK killing via interaction with CEA-related cell adhesion molecule 1. J Immunol 2005; 174:6692–701.PubMedGoogle Scholar
  120. 120.
    Gray-Owen SD, Blumberg RS. CEACAMl: Contact-dependent control of immunity. Nat Rev Immunol 2006; 6:433–46.PubMedCrossRefGoogle Scholar
  121. 121.
    Feng J, Garrity D, Call ME et al. Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors. Immunity 2005; 22:427–38.PubMedCrossRefGoogle Scholar
  122. 122.
    Garrity D, Call ME, Feng J et al. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Proc Natl Acad Sci USA 2005; 102:7641–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Call ME, Wucherpfennig KW. The T-cell receptor: Critical role of the membrane environment in receptor assembly and function. Annu Rev Immunol 2005; 23:101–25.PubMedCrossRefGoogle Scholar
  124. 124.
    Feng J, Call ME, Wucherpfennig KW. The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site. PLoS Biol 2006; 4:el42.CrossRefGoogle Scholar
  125. 125.
    Faure M, Long EO. KIR2DL4 (CD 158d), an NK cell-activating receptor with inhibitory potential. J Immunol 2002; 168:6208–14.PubMedGoogle Scholar
  126. 126.
    Estefania E, Flores R, Gomez-Lozano N et al. Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and ? lymphocyte subsets. J Immunol. 178; 2007:4402–10.PubMedGoogle Scholar
  127. 127.
    Sambrook JG, Bashirova A, Palmer S et al. Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates. Genome Res 2005; 15:25–35.PubMedCrossRefGoogle Scholar
  128. 128.
    Vance RE, Jamieson AM, Raulet DH. Recognition of the class 1b molecule Qa-l(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells. J Exp Med 1999; 190:1801–12.PubMedCrossRefGoogle Scholar
  129. 129.
    Saulquin X, Gastinel LN, Vivier E. Crystal structure of the human natural killer cell activating receptor Kir2Ds2 (Cdl58J). J Exp Med 2003; 197:933–8.PubMedCrossRefGoogle Scholar
  130. 130.
    Attrill H, Takazawa H, Witt S et al. The structure of siglec-7 in complex with sialosides: L eads for rational structure-based inhibitor design. Biochem J 2006; 397:271–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Swaminathan CP, Wais N, Vyas W et al. Entropically assisted carbohydrate recognition by a natural killer cell surface receptor. Chem Biochem 2004; 5:1571–75.Google Scholar
  132. 132.
    Miyazaki K, Ohmori K, Izawa M et al. Loss of disialyl Lewis(a), the ligand for lymphocyte inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) associated with increased sialyl Lewis(a) expression on human colon cancers. Cancer Res 2004; 64:4498–505.PubMedCrossRefGoogle Scholar
  133. 133.
    Eissmann P, Beauchamp L, Wooters J et al. Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244). Blood 2005; 105:4722–9.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Roberto Biassoni
    • 1
  1. 1.Molecular MedicineIstituto Giannina GasliniGenovaItaly

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