Abstract
NK cells express receptors characterized by opposite functions that finely regulate their activities. Among inhibitory receptors, some are specific for different groups of MHC class I alleles, while others are still orphan receptors. On the contrary, various activating receptors are involved in the triggering of NK‐mediated natural cytotoxicity. In general, their engagement induces human NK cells to kill target cells that are either HLA class I‐negative or ‐deficient. Thus, the process of NK cell triggering mediated by Natural Cytotoxicity Receptors can be mainly considered as a non MHC‐restricted mechanism. Here, a brief description of the molecular nature of these receptors, as well as, of their 3D‐structures and of the implications for ligand recognition, is given.
Keywords: Natural Killer (NK), Leucocyte Ig‐like Receptor Complex (LRC), Natural Cytotoxicity Receptors (NCRs), MHC, Inhibitory Receptors, Immunoglobulin Superfamily (Ig‐SF), Crystal Structure, Activating Receptors, Sialic acid‐binding Ig‐like lectin (Siglec)
References
- 1. Trincheri G., Biology of Natural Killer cell. Adv. Immunol., 47: 187–376, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Biron C.A., Activation and function of natural killer cell responses during viral infections, Curr. Opin. Immunol., 9: 24–34, 1997. [DOI] [PubMed] [Google Scholar]
- 3. Moretta A., Bottino C., Vitale M., Pende D., Biassoni R., Mingari M.C., Moretta L., Receptors for HLA‐class I molecules in human Natural Killer cells. Annu. Rev. Immunol., 14: 619–648, 1996. [DOI] [PubMed] [Google Scholar]
- 4. Long E.O., Barber D.F., Burshtyn D.N., Faure, M , Peterson M., Rajagopalan S., Renard V., Sandusky M., Stebbins C.C., Wagtmann N., Watzl C. Inhibition of natural killer cell activation signals by killer cell immunoglobulin‐like receptors (CD158). Immunol Rev., 181: 223–233, 2001. [DOI] [PubMed] [Google Scholar]
- 5. Biassoni R., Cantoni C., Pende D., Sivori S., Parolini S., Vitale M., Bottino C., Moretta A., Human natural killer cell receptors and coreceptors. Immunol. Rev., 181: 203–214, 2001. [DOI] [PubMed] [Google Scholar]
- 6. Biassoni R., Cantoni C., Bottino C., Moretta A., Human natural killer receptors and their ligands In: Curr Prot Immunol J. Wiley & Sons; 14.10. 1 ‐ 14.10.23, 2001. [DOI] [PubMed] [Google Scholar]
- 7. Lanier LL., NK cell receptors, Annu. Rev. Immunol. 16: 359–393, 1998. [DOI] [PubMed] [Google Scholar]
- 8. Natarajan K., Dimasi N., Wang J., Mariuzza R.A., Margulies D.H., Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination, Annu Rev Immunol. 20: 853–885, 2002. [DOI] [PubMed] [Google Scholar]
- 9. Long E.O., Regulation of immune responses through inhibitory receptors, Annu. Rev. Immunol. 17: 875–904, 1999. [DOI] [PubMed] [Google Scholar]
- 10. Moretta A., Bottino C., Vitale M., Pende D., Cantoni C., Biassoni R., Mingari M.C., Moretta L., Activating receptors and coreceptors involved in the Natural Cytotoxicity, Annu. Rev. Immunol. 19: 197–223, 2001. [DOI] [PubMed] [Google Scholar]
- 11. Garcia‐Lora A., Algarra I., Garrido F., MHC class I antigens, immune surveillance, and tumor immune escape, J Cell Physiol. 195: 346–355, 2003. [DOI] [PubMed] [Google Scholar]
- 12. Orange J.S., Fassett M.S., Koopman L.A., Boyson J.E., Strominger J.L., Viral evasion of natural killer cells, Nat. Immunol., 3: 1006–1012, 2002. [DOI] [PubMed] [Google Scholar]
- 13. Ljunggren H.G., Karre K., In search of the “missing self”. MHC molecules and NK cell recognition. Immunol. Today, 11: 237–244, 1990. [DOI] [PubMed] [Google Scholar]
- 14. Moretta A., Biassoni R., Bottino C., Mingari M.C., Moretta L., Natural cytotoxicity receptors that trigger human NK‐cell‐mediated cytolysis. Immunol. Today, 21: 228–234, 2000. [DOI] [PubMed] [Google Scholar]
- 15. Watzl C. The NKG2D receptor and its ligands‐recognition beyond the “missing self”, Microbes Infect., 5: 31–37, 2003. [DOI] [PubMed] [Google Scholar]
- 16. Cosman D., Mullberg J., Sutherland C.L., Chin W., Armitage R., Fanslow W., Kubin M., Chalupny N.J., ULBPs, novel MHC class I‐related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity, 14: 123–133, 2001. [DOI] [PubMed] [Google Scholar]
- 17. Chalupny N.J., Sutherland C.L., Lawrence W.A., Rein‐Weston A., Cosman D., ULBP4 is a novel ligand for human NKG2D”, Biochem. Biophys. Res. Comm., 305: 129–135, 2003. [DOI] [PubMed] [Google Scholar]
- 18. Diefenbach A., Raulet D.H., The innate immune response to tumors and its role in the induction of T‐cell immunity. Immunol. Rev., 188: 9–21, 2002. [DOI] [PubMed] [Google Scholar]
- 19. Kubin M.Z., Parsley D.L., Din W., Waugh J.Y., Davis‐Smith T., Smith C.A., Macduff B.M., Armitage R.J., Chin W., Cassiano L., Borges L., Petersen M., Trinchieri G., Goodwing R.G., Molecular cloning and biological characterization of NK cell activation‐inducing ligand, a counterstructure for CD48, Eur. J. Immunol., 29: 3466–3477, 1999. [DOI] [PubMed] [Google Scholar]
- 20. Bottino, C. , Castriconi R., Pende D., Rivera P., Nanni M., Carnemolla B., Cantoni C., Grassi J., Marcenaro S., Reymond N., Vitale M., Moretta L., Lopez M, Moretta A., 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, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Nicoll G., Avril T., Lock K., Furukawa K., Bovin N., Crocker P.R., Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via Siglec‐7‐dependent and ‐independent mechanisms, Eur. J. Immunol., 33: 1642–1648, 2003. [DOI] [PubMed] [Google Scholar]
- 22. Dimasi N., Swaminathan C.P., Attrill H., Wais N., Vyas V.V., Velikovsky C.A., Crocker P.R., Van F. Aalten D.M., Moretta L., Moretta A. Biassoni R. and Mariuzza R.A., Energetic basis of sialylated oligosaccharide recognition by the natural killer cell inhibitory receptor p75/AIRM1 (Submitted).
- 23. Meyaard L., van der Vuurst de Vries A.R., de Ruiter T., Lanier L.L., Phillips J.H., Clevers H., The epithelial cellular adhesion molecule (Ep‐CAM) is a ligand for the leukocyte‐associated immunoglobulin‐like receptor (LAIR), J. Exp. Med. 194: 101–112, 2001; Retraction 2003. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 24. Iizuka K., Naidenko O.V., Plougastel B.F.M., Fremont D.H., Yokoyama W.M., Genetically linked C‐type lectinrelated ligands for the NKRP1 family of natural killer cell receptors. Nat. Immunol., 8: 801–807, 2003. [DOI] [PubMed] [Google Scholar]
- 25. Mandelboim O., Lieberman N., Lev M., Paul L., Arnon T.I., Bushkin Y., Davis D.M., Strominger J.L., Yewdell J.W., Porgador A., Recognition of haemagglutinins on virus‐infected cells by NKp46 activates lysis by human NK cells. Nature, 409: 1055–1060, 2001. [DOI] [PubMed] [Google Scholar]
- 26. Arnon T.I., Lev M., Katz G., Chernobrov Y., Porgador A., Mandelboim O., Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur. J. Immunol., 31: 2680–2689, 2001. [DOI] [PubMed] [Google Scholar]
- 27. Augugliaro R., Parolini S., Castriconi R., Marcenaro E., Cantoni C., Nanni M., Moretta L., Moretta A., Bottino C., Selective cross‐talk among natural cytotoxicity receptors in human natural killer cells. Eur. J. Immunol., 33: 1235–1241, 2003. [DOI] [PubMed] [Google Scholar]
- 28. Carrington M., Norman P., The KIR Gene Cluster. National Library of Medicine (US), NCBI; 2003.
- 29. De Maria A., Biassoni R., Fogli M., Rizzi M., Cantoni C., Conte R., Costa P., Mavilio D., Cafaro A., Moretta A., Moretta L., Identification, molecular cloning and functional characterization of NKp46 and NKp30 Natural Cytotoxicity Receptors in Macaca fascicularis (Macaca Rhesus) NK cells. Eur. J. Immunol., 31: 3546–3556, 2001. [DOI] [PubMed] [Google Scholar]
- 30. Backman‐Petersson E., Miller J.R., Hollyoake M., Aguado B., Butcher G.W., Molecular characterization of the novel rat NK receptor 1C7, Eur. J. Immunol., 33: 342–351, 2003. [DOI] [PubMed] [Google Scholar]
- 31. Castriconi R, Cantoni C., Della Chiesa M., Vitale M., Marcenaro, E. , Conte, R. , Biassoni, R. , Bottino, C. , Moretta, L. , Moretta A., TGF1 inhibits the surface expression of the NKp30 and NKG2D triggering NK receptors: consequences on the NK‐mediated killing of dendritic cells, Proc. Natl. Acad. Sci. USA 100: 4120–4125, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Moretta A., Natural killer cells and dendritic cells: rendezvous in abused tissues, Nat Rev Immunol. 2: 957–964, 2002. [DOI] [PubMed] [Google Scholar]
- 33. Allcock R.J., Barrow A.D., Forbes S., Beck S., Trowsdale J., The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44, Eur J Immunol. 33: 567–577, 2003. [DOI] [PubMed] [Google Scholar]
- 34. Pende D., Cantoni C., Rivera P., Vitale M., Castriconi R., Marcenaro S., Nanni M., Biassoni R., Bottino C., Moretta A., Moretta L., Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotxicity receptors and capability of recognizing tumors of nonepithelial origin. Eur. J. Immunol., 31: 1076–1086.2001. [DOI] [PubMed] [Google Scholar]
- 35. Groh V., Rhinehart R., Secrist H., Bauer S., Grabstein K.H., Spies T., Broad tumor‐associated expression and recognition by tumor‐derived gamma delta T cells of MICA and MICB. Proc. Natl. Acad. Sci. USA, 96: 6879–6884, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Radaev S., Kattah M., Zou Z., Colonna M., Sun P.D., Making sense of the diverse ligand recognition by NKG2D, J. Immunol., 169: 6279–6285, 2002. [DOI] [PubMed] [Google Scholar]
- 37. Speckman R.A., Wright Daw J.A., Helms C., Duan S., Cao L., Taillon‐Miller P., Kwok P., Menter A., Bowcock A.M., Novel immunoglobulin suoerfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility, Hum. Genet. 112: 34–41, 2003. [DOI] [PubMed] [Google Scholar]
- 38. Chung DH, Seaman WE, Daws MR., Characterization of TREM‐3, an activating receptor on mouse macrophages: definition of a family of single Ig domain receptors on mouse chromosome 17, Eur J Immunol. 32: 59–66, 2002. [DOI] [PubMed] [Google Scholar]
- 39. Crocker PR., Siglecs: sialic‐acid‐binding immunoglobulin‐like lectins in cell‐cell interactions and signalling, Curr Opin Struct Biol. 12: 609–615, 2002. [DOI] [PubMed] [Google Scholar]
- 40. Yamaji T., Teranishi T., Alphey M.S., Crocker P.R., Hashimoto Y., A small region of the natural killer cell receptor, Siglec‐7, is responsible for its preferred binding to alpha 2,8‐disialyl and branched alpha 2,6‐sialyl residues. A comparison with Siglec‐9, J Biol Chem 277: 6324–6332, 2002. [DOI] [PubMed] [Google Scholar]
- 41. Mingari M.C., Vitale C., Romagnani C., Falco M., Moretta L., p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells, Immunol. Rev., 181: 260–268, 2001. [DOI] [PubMed] [Google Scholar]
- 42. Cantoni C., Ponassi M., Biassoni R., Conte R., Spallarossa A., Moretta A., Moretta L. Bolognesi M., Bordo D., The three‐dimensional structure of NK cell receptor NKp44, a triggering partner in natural cytotoxicity. Structure, 11: 725–734, 2003. [DOI] [PubMed] [Google Scholar]
- 43. Ponassi M., Cantoni C., Biassoni R., Conte R., Spallarossa A., Pesce A., Moretta A., Moretta L., Bolognesi M., Bordo D., Structure of the human NK cell triggering receptor NKp46 ectodomain. Biochem. Biophys. Res. Comm., 309: 317–323, 2003. [DOI] [PubMed] [Google Scholar]
- 44. Foster CE, Colonna M, Sun PD Crystal structure of the human NK cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors. J. Biol. Chem 45. (in press). [DOI] [PubMed] [Google Scholar]
- 45. Alphey M.S., Attrill H., Crocker P.R., van Aalten D.M., High resolution crystal structures of Siglec‐7. Insights into ligand specificity in the Siglec family. J. Biol. Chem., 278: 3372–3377, 2003. [DOI] [PubMed] [Google Scholar]
- 46. May A.P., Robinson R.C., Vinson M., Crocker P.R., Jones E.Y., Crystal structure of the N‐terminal domain of sialoadhesin in complex with 3′ sialyllactose at 1.85 A resolution. Mol. Cell., 1: 719–728, 1998. [DOI] [PubMed] [Google Scholar]