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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Killer Cells

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Disease relevance of Killer Cells


High impact information on Killer Cells

  • A transcript map of the region identified 19 genes, including members of the killer cell lectin-like receptor family a (Klra, formerly Ly49; refs. 9-12), which encode inhibitory or activating NK cell receptors that interact with MHC class I molecules [6].
  • Here, a mechanism by which killer cells resist their own toxin is shown: internal toxin inhibits TOK1 channels and suppresses activation by external toxin [7].
  • The human p58 natural killer-cell inhibitory receptor clone 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA-Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor receptor clone 43 [8].
  • ICAM-2 redistributed by ezrin as a target for killer cells [9].
  • Interactions of such oligosaccharides on the target cell surface with NKR-P1 on the killer cell surface are crucial both for target cell recognition and for delivery of stimulatory or inhibitory signals linked to the NK cytolytic machinery [10].

Chemical compound and disease context of Killer Cells


Biological context of Killer Cells


Anatomical context of Killer Cells

  • Although it is structurally related to human killer cell inhibitory receptors, LAIR-1 does not appear to recognize human leukocyte antigen (HLA) class I molecules and thus represents a novel HLA class I-independent mechanism of NK cell regulation [21].
  • The HNK-1 antibody known to define a subpopulation of human lymphocytes with natural killer and killer cell activities was shown to detect a common neuroectodermal antigen [22].
  • TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors [23].
  • We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell-mediated cytotoxicity [24].
  • Since killer-specific esterases and channel-forming proteins can be demonstrated in in vitro cell lines, it is important to ascertain that the described esterase and channel-forming proteins are also present in killer cells from in vivo sources [25].

Associations of Killer Cells with chemical compounds

  • Glucose-dependent insulin release from genetically engineered K cells [26].
  • Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor [27].
  • Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents [28].
  • Neuraminidase-augmented anticarcinoembryonic antigen (CEA)-complement lysis of human colon tumor cells: lack of correlation with anti-CEA-mediated K-cell lysis and iodine-125 binding [29].
  • This recovery of cell K+ content was inhibited, in an additive manner, by quinine and furosemide [30].

Gene context of Killer Cells

  • Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer [31].
  • We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4 [32].
  • NKB1 is one member of a growing family of killer cell inhibitory receptors (KIR) [33].
  • HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1 [34].
  • CONCLUSIONS: Our findings strongly suggest that expression of B7-1, B7-2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM [35].

Analytical, diagnostic and therapeutic context of Killer Cells


  1. Amelioration of B16F10 melanoma lung metastasis in mice by a combination therapy with indomethacin and interleukin 2. Parhar, R.S., Lala, P.K. J. Exp. Med. (1987) [Pubmed]
  2. Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. Brugnara, C., Gee, B., Armsby, C.C., Kurth, S., Sakamoto, M., Rifai, N., Alper, S.L., Platt, O.S. J. Clin. Invest. (1996) [Pubmed]
  3. Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu's arteritis. Seko, Y., Minota, S., Kawasaki, A., Shinkai, Y., Maeda, K., Yagita, H., Okumura, K., Sato, O., Takagi, A., Tada, Y. J. Clin. Invest. (1994) [Pubmed]
  4. Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat. Tseng, C.C., Kieffer, T.J., Jarboe, L.A., Usdin, T.B., Wolfe, M.M. J. Clin. Invest. (1996) [Pubmed]
  5. Absence of H-2 antigens capable of reacting with cytotoxic T cells on a teratoma line expressing a T/t locus antigen. Forman, J., Vitetta, E.S. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  6. Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily. Lee, S.H., Girard, S., Macina, D., Busà, M., Zafer, A., Belouchi, A., Gros, P., Vidal, S.M. Nat. Genet. (2001) [Pubmed]
  7. Immunity to K1 killer toxin: internal TOK1 blockade. Sesti, F., Shih, T.M., Nikolaeva, N., Goldstein, S.A. Cell (2001) [Pubmed]
  8. Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors. Fan, Q.R., Mosyak, L., Winter, C.C., Wagtmann, N., Long, E.O., Wiley, D.C. Nature (1997) [Pubmed]
  9. ICAM-2 redistributed by ezrin as a target for killer cells. Helander, T.S., Carpén, O., Turunen, O., Kovanen, P.E., Vaheri, A., Timonen, T. Nature (1996) [Pubmed]
  10. Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Bezouska, K., Yuen, C.T., O'Brien, J., Childs, R.A., Chai, W., Lawson, A.M., Drbal, K., Fiserová, A., Pospísil, M., Feizi, T. Nature (1994) [Pubmed]
  11. Fluctuations in the expression of a glycolipid antigen associated with differentiation of melanoma cells monitored by a monoclonal antibody, Leo Mel 3. Werkmeister, J.A., Triglia, T., Mackay, I.R., Dowling, J.P., Varigos, G.A., Morstyn, G., Burns, G.F. Cancer Res. (1987) [Pubmed]
  12. Killer cell systems of cynomolgus monkeys experimentally infected with HTLV-1. Yoshimura, N., Nakamura, H., Honjo, S., Akiyama, N., Hayami, M. J. Immunol. (1988) [Pubmed]
  13. Perforin-mediated lysis of tumor cells by Mycobacterium bovis Bacillus Calmette-Guérin-activated killer cells. Brandau, S., Suttmann, H., Riemensberger, J., Seitzer, U., Arnold, J., Durek, C., Jocham, D., Flad, H.D., Böhle, A. Clin. Cancer Res. (2000) [Pubmed]
  14. Effect of cortisone acetate on effector cells for antibody-mediated cytotoxicity in mouse and rat. Purves, E.C., Brown, K. Transplantation (1978) [Pubmed]
  15. Immunoregulation during acute infection with Epstein-Barr virus: dynamics of interferon and 2',5'-oligoadenylate synthetase activity. Brewster, F.E., Byron, K.S., Sullivan, J.L. J. Infect. Dis. (1985) [Pubmed]
  16. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Binstadt, B.A., Brumbaugh, K.M., Dick, C.J., Scharenberg, A.M., Williams, B.L., Colonna, M., Lanier, L.L., Kinet, J.P., Abraham, R.T., Leibson, P.J. Immunity (1996) [Pubmed]
  17. Regulation of the growth and functions of cloned murine large granular lymphocyte lines by resident macrophages. Minato, N., Amagai, T., Yodoi, J., Diamanstein, T., Kano, S. J. Exp. Med. (1985) [Pubmed]
  18. T-cell killing of target cells induced by hybrid antibodies: comparison of two bispecific monoclonal antibodies. Clark, M.R., Waldmann, H. J. Natl. Cancer Inst. (1987) [Pubmed]
  19. Natural killer cell acceptance of H-2 mismatch bone marrow grafts in transgenic mice expressing HLA-Cw3 specific killer cell inhibitory receptor. Cambiaggi, A., Verthuy, C., Naquet, P., Romagné, F., Ferrier, P., Biassoni, R., Moretta, A., Moretta, L., Vivier, E. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. AKT3, a phloem-localized K+ channel, is blocked by protons. Marten, I., Hoth, S., Deeken, R., Ache, P., Ketchum, K.A., Hoshi, T., Hedrich, R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Meyaard, L., Adema, G.J., Chang, C., Woollatt, E., Sutherland, G.R., Lanier, L.L., Phillips, J.H. Immunity (1997) [Pubmed]
  22. HNK-1 antibody detects an antigen expressed on neuroectodermal cells. Lipinski, M., Braham, K., Caillaud, J.M., Carlu, C., Tursz, T. J. Exp. Med. (1983) [Pubmed]
  23. TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. Burns, G.F., Triglia, T., Werkmeister, J.A., Begley, C.G., Boyd, A.W. J. Exp. Med. (1985) [Pubmed]
  24. Modulation of natural killer cell cytotoxicity in human cytomegalovirus infection: the role of endogenous class I major histocompatibility complex and a viral class I homolog. Leong, C.C., Chapman, T.L., Bjorkman, P.J., Formankova, D., Mocarski, E.S., Phillips, J.H., Lanier, L.L. J. Exp. Med. (1998) [Pubmed]
  25. High activity of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase and cytolytic perforin in cloned cell lines is not demonstrable in in-vivo-induced cytotoxic effector cells. Dennert, G., Anderson, C.G., Prochazka, G. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  26. Glucose-dependent insulin release from genetically engineered K cells. Cheung, A.T., Dayanandan, B., Lewis, J.T., Korbutt, G.S., Rajotte, R.V., Bryer-Ash, M., Boylan, M.O., Wolfe, M.M., Kieffer, T.J. Science (2000) [Pubmed]
  27. Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor. Burshtyn, D.N., Scharenberg, A.M., Wagtmann, N., Rajagopalan, S., Berrada, K., Yi, T., Kinet, J.P., Long, E.O. Immunity (1996) [Pubmed]
  28. Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms. Bruley-Rosset, M., Hercend, T., Martinez, J., Rappaport, H., Mathé, G. J. Natl. Cancer Inst. (1981) [Pubmed]
  29. Neuraminidase-augmented anticarcinoembryonic antigen (CEA)-complement lysis of human colon tumor cells: lack of correlation with anti-CEA-mediated K-cell lysis and iodine-125 binding. Tompkins, W.A., Schmale, J.D., Mock, R., Tick, N.T., Lock, T., Sidell, N., Palmer, J.L. J. Natl. Cancer Inst. (1979) [Pubmed]
  30. Coordinated regulation of intracellular K+ in the proximal tubule: Ba2+ blockade down-regulates the Na+,K+-ATPase and up-regulates two K+ permeability pathways. Kone, B.C., Brady, H.R., Gullans, S.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  31. Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. Wagtmann, N., Rajagopalan, S., Winter, C.C., Peruzzi, M., Long, E.O. Immunity (1995) [Pubmed]
  32. Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex. Fan, Q.R., Long, E.O., Wiley, D.C. Nat. Immunol. (2001) [Pubmed]
  33. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C. Fry, A.M., Lanier, L.L., Weiss, A. J. Exp. Med. (1996) [Pubmed]
  34. HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Lee, N., Llano, M., Carretero, M., Ishitani, A., Navarro, F., López-Botet, M., Geraghty, D.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  35. Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy. Seko, Y., Takahashi, N., Ishiyama, S., Nishikawa, T., Kasajima, T., Hiroe, M., Suzuki, S., Ishiwata, S., Kawai, S., Azuma, M., Yagita, H., Okumura, K., Yazaki, Y. Circulation (1998) [Pubmed]
  36. Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes. Blanckmeister, C.A., Yamamoto, K., Davis, M.M., Hämmerling, G.J. J. Exp. Med. (1985) [Pubmed]
  37. Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression. Nakajima, F., Khanna, A., Xu, G., Lagman, M., Haschemeyer, R., Mouradian, J., Wang, J.C., Stenzel, K.H., Rubin, A.L., Suthanthiran, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  38. Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor. Tso, C.L., Zisman, A., Pantuck, A., Calilliw, R., Hernandez, J.M., Paik, S., Nguyen, D., Gitlitz, B., Shintaku, P.I., de Kernion, J., Figlin, R., Belldegrun, A. Cancer Res. (2001) [Pubmed]
  39. Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. Hayami, K., Fukuta, D., Nishikawa, Y., Yamashita, Y., Inui, M., Ohyama, Y., Hikida, M., Ohmori, H., Takai, T. J. Biol. Chem. (1997) [Pubmed]
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