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NK Cell Activating Receptors and Tumor Recognition in Humans

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 298))

Abstract

Natural killer (NK) cells have been known for many years as the lymphocyte subset characterized by the highest cytolytic potential against virus-infected and tumor-transformed cells. A surprisingly high number of surface molecules have been recognized that regulate human NK cell function. These include MHC-specific inhibitory receptors, which impair NK cells’ ability to attack normal self-tissues, and activating receptors and coreceptors that allowthemto recognize and kill transformed cells. The recent identification of some of the cellular ligands specifically recognized by these receptors/coreceptors contributes to elucidation of the mystery of the role played by NK cells in immune responses.

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References

  1. Biron, C.A. et al. (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu. Rev. Immunol. 17, 189–220.

    Article  CAS  PubMed  Google Scholar 

  2. Parham, P. (2003) Immunogenetics of killer-cell immunoglobulin-like receptors. Tissue Antigens 62, 194–200.

    Article  CAS  PubMed  Google Scholar 

  3. Moretta, L. and Moretta, A. (2004) Killer immunoglobulin-like receptors. Curr. Opin. Immunol. 16, 626–633.

    Article  CAS  PubMed  Google Scholar 

  4. Lopez-Botet, M. et al. (2000) NK cell recognition of non-classical HLA class I molecules. Semin. Immunol. 12, 109–119.

    Article  CAS  PubMed  Google Scholar 

  5. Algarra, I. et al. (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class Imolecules: implications for tumor immune escape. Cancer Immunol. Immunother. 53, 904–910.

    Article  CAS  PubMed  Google Scholar 

  6. Alcami, A. and Koszinowski, U.H. (2000) Viral mechanisms of immune evasion. Immunol. Today 21, 447–455.

    Article  CAS  PubMed  Google Scholar 

  7. Moretta, A. et al. (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Rev. Immunol. 19, 197–223.

    Article  CAS  PubMed  Google Scholar 

  8. Lanier, L.L. (2003) Natural killer cell receptor signaling. Curr. Opin. Immunol. 15, 308–314.

    Article  CAS  PubMed  Google Scholar 

  9. Bottino C. et al. (2005) Cellular ligands of activating NK receptors. Trends Immunol. 26, 221–226.

    Article  CAS  PubMed  Google Scholar 

  10. Moretta, A. et al. (2000) Natural cytotoxicity receptors that trigger human NK-mediated cytolysis. Immunol. Today 21, 228–234.

    Article  CAS  PubMed  Google Scholar 

  11. Augugliaro, R. et al. (2003) Selective cross-talk among natural cytotoxicity receptors in human natural killer cells. Eur. J. Immunol. 33, 1235–1241.

    Article  CAS  PubMed  Google Scholar 

  12. Sivori, S. et al. (2000) Involvement of natural cytotoxicity receptors in human natural killer cell mediated lysis of neuroblastoma and glyoblastoma cell lines. J. Neuroimmunol. 107, 220–225.

    Article  CAS  PubMed  Google Scholar 

  13. Castriconi, R. et al. (2004) Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAM-1/PVR interaction. Cancer Res. 64, 9180–9184.

    Article  CAS  PubMed  Google Scholar 

  14. Pende, D. et al. (2005) Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112). Blood 105, 2066–2073.

    Article  CAS  PubMed  Google Scholar 

  15. Nowbakht, P. et al. (2005) Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. Blood 105, 3615–3622.

    Article  CAS  PubMed  Google Scholar 

  16. Moretta, A. (2002) Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat. Rev. Immunol. 2, 957–964.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Bottino, C. et al. (2001) NTB-A, a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative diseases. J. Exp. Med. 194, 235–246.

    Article  CAS  PubMed  Google Scholar 

  19. Vitale, M. et al. (2001) Identification of NKp80, a novel triggering molecule expressed by human natural killer cells. Eur. J. Immunol. 31, 233–242

    Article  CAS  PubMed  Google Scholar 

  20. Marcenaro, E. et al. (2003) CD59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity. Eur. J. Immunol. 33, 3367–3376.

    Article  CAS  PubMed  Google Scholar 

  21. Nakajima, H. et al. (1999) Activating interactions in human NK cell recognition: the role of 2B4-CD48. Eur J Immunol. 29, 1676–1683.

    Article  CAS  PubMed  Google Scholar 

  22. Falco, M. et al. (2004) Homophilic interaction of NTBA, a member of the CD2 molecular family: induction of cytotoxicity and cytokine release in human NK cells. Eur J Immunol. 34, 1663–1672.

    Article  CAS  PubMed  Google Scholar 

  23. Parolini, S. et al. (2000) 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. 192, 337–346.

    Article  CAS  PubMed  Google Scholar 

  24. Eissmann, P. et al. (2005) Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244). Blood 105, 4722–4729.

    Article  CAS  PubMed  Google Scholar 

  25. Loic, D. et al. (2005) SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells. DOI 10.1182/blood-2004-08-3269

    Google Scholar 

  26. Sivori S. et al. (2002) Early expression of triggering receptors and regulatory role of 2B4 in human NK cell precursors undergoing in vitro differentiation. P. Natl. Acad. Sci. USA 99, 4526–4531.

    Article  CAS  Google Scholar 

  27. Bottino C, et al. (2000) 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. 30, 3718–3722.

    Article  CAS  PubMed  Google Scholar 

  28. Li, P., et al., 2001. Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat. Immunol. 2, 443–451.

    Google Scholar 

  29. Cosman, D., et al., 2001. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14, 123–133.

    Google Scholar 

  30. Cerwenka, A. and Lanier, L.L. (2003) NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer. Tissue Antigens 61, 335–343.

    Article  CAS  PubMed  Google Scholar 

  31. Diefenbach, A. et al. (2002) Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol. 3, 1142–1149.

    Article  CAS  PubMed  Google Scholar 

  32. Zompi, S. et al. (2003) NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol. 4, 565–572

    Article  CAS  PubMed  Google Scholar 

  33. Andre, P. et al. (2004) Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors. Eur. J. Immunol. 34, 961–971.

    Article  CAS  PubMed  Google Scholar 

  34. Bottino, C. et al. (2003) Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198, 557–567.

    Article  CAS  PubMed  Google Scholar 

  35. Kojima, H., et al (2003) CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells. J. Biol. Chem. 278:36748–36753.

    Article  CAS  PubMed  Google Scholar 

  36. Reymond, N. et al. (2004) DNAM-1 and PVR regulate monocyte migration through endothelial junctions. J. Exp. Med. 199, 1331–1341.

    Article  CAS  PubMed  Google Scholar 

  37. Oda T. et al. (2004) Ligand stimulation of CD155a inhibits cell adhesion and enhances migration of fibroblasts. Biochem. Biophys. Res. Commun. 319, 1253–1264.

    Article  CAS  PubMed  Google Scholar 

  38. Barber, D.F. et al. (2004) LFA-1 contributes an early signal for NK cell cytotoxicity. J. Immunol. 173, 3653–3659.

    CAS  PubMed  Google Scholar 

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Correspondence to A. Moretta .

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© 2006 Springer-Verlag Berlin Heidelberg

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Bottino, C., Moretta, L., Moretta, A. (2006). NK Cell Activating Receptors and Tumor Recognition in Humans. In: Compans, R., et al. Immunobiology of Natural Killer Cell Receptors. Current Topics in Microbiology and Immunology, vol 298. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27743-9_9

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