Immunologic Research

, Volume 27, Issue 2–3, pp 539–548 | Cite as

Structure and function of natural-killer-cell receptors



The function of natural-killer (NK) cells is modulated by the balance between a number of activating and inhibitory receptors. Killer immunoglobulinlike receptors (KIRs) are mostly inhibitory receptors. They play a critical role in recognizing self-class-I major histocompatibility complex (MHC) molecules and thus protect healthy host cells from NK-targeted lysis. In contrast, both NKG2D and CD16 are activating NK receptors that trigger the NK-cell lysis of various tumor and virally infected cells through either direct ligand engagement or antibody-dependent cellular cytotoxicity (ADCC). Through structural studies of members of these distinct receptor families, in particular, the structure and recognition between KIR2DL2 and HLA-Cw3, that between NKG2D and ULBP3, and that between CD16 and IgG Fc, considerable understandings have been achieved about their function and their ligand recognition.

Key Words

KIR NKG2D Fc receptors Crystal structure Immunoreceptors NK receptors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lanier LL: Annu Rev Immunol 1998;16:359–393.PubMedCrossRefGoogle Scholar
  2. 2.
    Long EO: Annu Rev Immunol 1999;17:875–904.PubMedCrossRefGoogle Scholar
  3. 3.
    Colonna M, Samaridis J: Science 1995;268:405–408.PubMedCrossRefGoogle Scholar
  4. 4.
    D'Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH, Lanier LL: J Immunol 1995; 155:2306–2310.PubMedGoogle Scholar
  5. 5.
    Steffens U, Vyas Y, Dupont B, Selvakumar A: Tissue Antigens 1998;51:398–413.PubMedCrossRefGoogle Scholar
  6. 6.
    Wilson MJ, Torkar M, Trowsdale J: Tissue Antigens 1997;49:574–579.PubMedCrossRefGoogle Scholar
  7. 7.
    Khakoo SI, Rajalingam R, Shum BP, Weidenbach K, Flodin L, Muir DG, et al.: Immunity 2000;12:687–698.PubMedCrossRefGoogle Scholar
  8. 8.
    Samaridis J, Colonna M: Eur J Immunol 1997;27:660–665.PubMedCrossRefGoogle Scholar
  9. 9.
    Borges L, Hsu ML, Fanger N, Kubin M, Cosman D: J Immunol 1997;159:5192–5196.PubMedGoogle Scholar
  10. 10.
    Colonna M, Navano F, Bellon T, Llano M, Garcia P, Samaridis J, et al.: J Exp Med 1997;186:1809–1818.PubMedCrossRefGoogle Scholar
  11. 11.
    Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, et al.: Immunity 1997;7:283–290.PubMedCrossRefGoogle Scholar
  12. 12.
    Arm JP, Gurish MF, Reynolds DS, Scott HC, Gartner CS, Austen KF, et al.: J Biol Chem 1991;266:15,966–15,973.Google Scholar
  13. 13.
    Kubagawa H, Burrows PD, Cooper MD: Proc Natl Acad Sci USA 1997;94:5261–5266.PubMedCrossRefGoogle Scholar
  14. 14.
    Hayami K, Fukuta D, Nishikawa Y, Yamashita Y, Inui M, Ohyama Y, et al.: J Biol Chem 1997;272:7320–7327.PubMedCrossRefGoogle Scholar
  15. 15.
    Boyington JC, Motyka SA, Schuck P, Brooks AG, Sun PD: Nature 2000;405:537–543.PubMedCrossRefGoogle Scholar
  16. 16.
    Ding YH, Smith KJ, Garboczi DN, Utz U, Biddison WE, Wiley DC: Immunity 1998;8:403–411.PubMedCrossRefGoogle Scholar
  17. 17.
    Garcia KC, Degano M, Stanfield RL, Brunmark A, Jackson MR, Peterson PA, et al.: Science 1996; 274:209–219.PubMedCrossRefGoogle Scholar
  18. 18.
    Wagtmann N, Biassoni R, Cantoni C, Verdiani S, Malnati MS, Vitale M, et al.: Immunity 1995;2:439–449.PubMedCrossRefGoogle Scholar
  19. 19.
    Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al.: Science 1999;285:727–729.PubMedCrossRefGoogle Scholar
  20. 20.
    Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, et al.: Science 1999;285:730–732.PubMedCrossRefGoogle Scholar
  21. 21.
    Groh V, Rhinehart R, Randolph-Habecker J, Topp MS, Riddell SR, Spies T: (2001) Nat Immunol 2001;2:255–260.PubMedCrossRefGoogle Scholar
  22. 22.
    Das H, Groh V, Kuijl C, Sugita M, Morita CT, Spies T, et al.: Immunity 2001;15:83–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Cerwenka A, Bakker AB, McClanahan T, Wagner J, Wu J, Phillips JH, et al.: Immunity 2000;12:721–727.PubMedCrossRefGoogle Scholar
  24. 24.
    Diefenbach A, Jamieson AM, Liu SD, Shastri N, Raulet DH: Nat Immunol 2000;1:119–126.PubMedCrossRefGoogle Scholar
  25. 25.
    Li P, Willie ST, Bauer S, Morris DL, Spies T, Strong RK: Immunity 1999;10:577–584.PubMedCrossRefGoogle Scholar
  26. 26.
    Cosman D, Mullberg J, Sutherland CL, Chin W, Annitage R, Fanslow W, et al.: Immunity 2001;14:123–133.PubMedCrossRefGoogle Scholar
  27. 27.
    Radaev S, Rostro B, Brooks AG, Colonna M, Sun PD: Immunity 2001;15:1–20.CrossRefGoogle Scholar
  28. 28.
    Lawrence MC, Colman PM: J Mol Biol 1993;234:946–950.PubMedCrossRefGoogle Scholar
  29. 29.
    Li P, Morris DL, Willcox BE, Steinle A, Spies T, Strong RK: Nat Immunol 2001;2:443–451.PubMedGoogle Scholar
  30. 30.
    Boyington JC, Motyka SA, Schuck P, Brooks AG, Sun PD: Nature 2000;405:537–543.PubMedCrossRefGoogle Scholar
  31. 31.
    Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC: Nature 1996;384:134–141.PubMedCrossRefGoogle Scholar
  32. 32.
    Garcia KC, Degano M, Stanfield RL, Brunmark A, Jackson MR, Peterson PA, et al.: Science 1996;274:209–219.PubMedCrossRefGoogle Scholar
  33. 33.
    Reinherz EL, Tan K, Tang L, Kern P, Liu J, Xiong Y, et al.: Science 1999;286:1913–1921.PubMedCrossRefGoogle Scholar
  34. 34.
    Garcia KC, Degano M, Pease LR, Huang M, Peterson PA, Teyton L, et al.: Science 1998;279:1166–1172.PubMedCrossRefGoogle Scholar
  35. 35.
    Radaev S, Motyka S, Fridman WH, Sautes-Fridman C, Sun PD. J Biol Chem 2001;276:16,469–16,477.Google Scholar
  36. 36.
    Wang JH, Smolyar A, Tan K, Liu JH, Kim M, Sun ZY, et al.: Cell 1999;97:791–803.PubMedCrossRefGoogle Scholar
  37. 37.
    Fridman WH: Curr Opin Immunol 1993;5:355–360.PubMedCrossRefGoogle Scholar
  38. 38.
    Ravetch JV, Clynes RA: Annu Rev Immunol 1998;16:421–432.PubMedCrossRefGoogle Scholar
  39. 39.
    Hulett MD, Hogarth PM: Adv Immunol 1994;57:1–127.PubMedCrossRefGoogle Scholar
  40. 40.
    Daeron M: Int Rev Immunol 1997;16:1–27.PubMedGoogle Scholar
  41. 41.
    Radaev S, Fridman W-H, Sautes-Fridman C, Sun PD: The structure of a human type III Fecgamma receptorincomplex with Fc. J Biol Chem 2001;276:16,469–16,477.Google Scholar
  42. 42.
    Sondermann P, Huber R, Oosthuizen V, Jacob U: Nature 2000; 406:267–273.PubMedCrossRefGoogle Scholar
  43. 43.
    Tamm A, Schmidt RE: Int Rev Immunol 1997;16:57–85.PubMedGoogle Scholar
  44. 44.
    Tamm A, Kister A, Nolte KU, Gessner JE, Schmidt RE: J Biol Chem 1996;271:3659–3666.PubMedCrossRefGoogle Scholar
  45. 45.
    Hibbs ML, Tolvanen M, Carpen O: J Immunol 1994;152:4466–4474.PubMedGoogle Scholar
  46. 46.
    Radaev S, Sun PD: J Biol Chem 2001;276:16,478–16,483.Google Scholar
  47. 47.
    Vaughan JH: Arthritis Rheum. 1993;36:1–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Jefferis R, Lund J, Pound JD: Immunol Rev 1998;163:59–76.PubMedCrossRefGoogle Scholar
  49. 49.
    Kulczycki A Jr, Vallina VL: Mol Immunol 1981;18:723–731.PubMedCrossRefGoogle Scholar
  50. 50.
    Lund J, Tanata T, Takahashi N, Sarmay G, Arata Y, Jefferis R: Mol Immunol 1990;27:1145–1153.PubMedCrossRefGoogle Scholar
  51. 51.
    Garman SC, Wurzburg BA, Tarchevskaya SS, Kinet JP, Jardetzky TS: Nature 2000;406:259–266.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  1. 1.Structural Immunology Section Laboratory of Immunogenetics National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockville

Personalised recommendations