The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

KLRD1  -  killer cell lectin-like receptor subfamily...

Homo sapiens

Synonyms: CD94, KP43, Killer cell lectin-like receptor subfamily D member 1, NK cell receptor, Natural killer cells antigen CD94
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of KLRD1


High impact information on KLRD1

  • Because Qa-1 also binds to self Qdm peptides that trigger NK (CD94/ NKG2) receptors on CD8(+) T cells, the machinery for homeostatic regulation of regulatory CD8(+) T cells can be envisioned [6].
  • HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C [7].
  • The fact that a very small subset of NK cells (approximately equal to 10%) as well as some NK clones (JT11) does not express CD2 argues against a potential role for CD2 as the NK cell receptor [8].
  • However, the function and ligand(s) of the NK cell gene complex-encoded human NK cell receptor NKp80 remain elusive [9].
  • The structures of activating and inhibitory NK cell surface receptors and their complexes with the ligands determined to date, including killer immunoglobulin-like receptors (KIRs) and their complexes with HLA molecules, CD94, Ly49A, and its complex with H-2Dd, and NKG2D receptors and their complexes with class I MHC homologs, are reviewed here [10].

Biological context of KLRD1


Anatomical context of KLRD1

  • A subset of HLA class I alleles has been shown to inhibit killing by CD94/NKG2A+ NK-cell clones [7].
  • It interacts with CD94/NKG2 receptors expressed on the surface of natural killer (NK) cells and T cell subsets [15].
  • On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in mixed lymphocyte culture (MLC) and have high transforming growth factor (TGF)-beta1- but low IL-2- producing capacity [2].
  • These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic phytohemagglutinin (PHA) blasts in vitro [2].
  • Taken together the data support that the interaction of CD94/NKG2C with HCMV-infected fibroblasts, concomitant to the inhibition of human leukocyte antigen (HLA) class I expression, promotes an outgrowth of CD94/NKG2C(+) NK cells [16].

Associations of KLRD1 with chemical compounds

  • Confocal microscopy was used to determine whether SH2 domain-bearing tyrosine phosphatase-1 and CD94/NKG2A colocalized intracellularly after receptor ligation [17].
  • Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily [18].
  • Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway [19].
  • Interestingly, when low concentrations of PGE2 or 8-CPT-cAMP were present during the culture, the proportion of CD8+ T cells expressing CD94/NKG2A was two- to five-fold higher [19].
  • Conversely, CHX blocked CD94 mRNA expression in PMA-stimulated cells, demonstrating that this process is dependent on new protein synthesis [20].

Physical interactions of KLRD1

  • This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity [21].
  • These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors [22].
  • The CD94/NKG2 C-type lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules [23].

Regulatory relationships of KLRD1


Other interactions of KLRD1

  • Surface expression of HLA-E was enough to protect target cells from lysis by CD94/NKG2A+ NK-cell clones [7].
  • In the absence of lymphocyte-stimulating cytokines or when contact with AFT024 was prohibited, NK cell progeny were killer immunoglobulinlike receptor (KIR) and CD94 lectin receptor negative [29].
  • Purified CD56(+) populations stimulated with HCMV-infected cells did not proliferate, but the expansion of the CD94/NKG2C(+) subset was detected in the presence of interleukin-15 (IL-15) [16].
  • The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells [25].
  • However, a conserved 24-amino acid sequence, present in all members of the NKG2 family, suggests that NKG2-F is also able to form heterodimers with CD94 [30].

Analytical, diagnostic and therapeutic context of KLRD1

  • By contrast, NK clones bearing the homologous CD94/p39 receptor are triggered upon its ligation by CD94-specific mAbs [31].
  • The immunoprecipitation of CD94 heterodimer showed a 39-kDa band with a similar m.w. to the activatory heterodimer found on some NK clones [32].
  • Thus, triggering NK cell receptor monitoring on macaque NK cells is possible and could provide a valuable tool for assessing NK cell function during experimental infections and for exploring possible differences in immune correlates of protection in humans compared with cynomolgus and rhesus macaques undergoing different vaccination strategies [33].
  • Analysis of the expression of the various HLA class I-specific inhibitory NK receptors revealed the presence of high proportions of CD94/ NKG2-A+ cells, while the NK receptors belonging to the Ig superfamily were undetectable both by immunofluorescence and by RT-PCR analysis [34].
  • Furthermore, their ability to bind solubilized immunoaffinity-purified HLA class I antigens, either alone or following association with CD94 lectin domains, was evaluated using flow cytometry and Western blot analyses [35].


  1. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Gumá, M., Angulo, A., Vilches, C., Gómez-Lozano, N., Malats, N., López-Botet, M. Blood (2004) [Pubmed]
  2. Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Tanaka, J., Toubai, T., Tsutsumi, Y., Miura, Y., Kato, N., Umehara, S., Kahata, K., Mori, A., Toyoshima, N., Ota, S., Kobayashi, T., Kobayashi, M., Kasai, M., Asaka, M., Imamura, M. Blood (2004) [Pubmed]
  3. Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis. Dulphy, N., Rabian, C., Douay, C., Flinois, O., Laoussadi, S., Kuipers, J., Tamouza, R., Charron, D., Toubert, A. Int. Immunol. (2002) [Pubmed]
  4. Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population. Hikami, K., Tsuchiya, N., Yabe, T., Tokunaga, K. Genes Immun. (2003) [Pubmed]
  5. IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. Malmberg, K.J., Levitsky, V., Norell, H., de Matos, C.T., Carlsten, M., Schedvins, K., Rabbani, H., Moretta, A., Söderström, K., Levitskaya, J., Kiessling, R. J. Clin. Invest. (2002) [Pubmed]
  6. The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1. Jiang, H., Chess, L. Annu. Rev. Immunol. (2000) [Pubmed]
  7. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Braud, V.M., Allan, D.S., O'Callaghan, C.A., Söderström, K., D'Andrea, A., Ogg, G.S., Lazetic, S., Young, N.T., Bell, J.I., Phillips, J.H., Lanier, L.L., McMichael, A.J. Nature (1998) [Pubmed]
  8. Characterization of functional surface structures on human natural killer cells. Ritz, J., Schmidt, R.E., Michon, J., Hercend, T., Schlossman, S.F. Adv. Immunol. (1988) [Pubmed]
  9. Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction. Welte, S., Kuttruff, S., Waldhauer, I., Steinle, A. Nat. Immunol. (2006) [Pubmed]
  10. Structure and function of natural killer cell surface receptors. Radaev, S., Sun, P.D. Annual review of biophysics and biomolecular structure. (2003) [Pubmed]
  11. NK cell CD94/NKG2A inhibitory receptors are internalized and recycle independently of inhibitory signaling processes. Borrego, F., Kabat, J., Sanni, T.B., Coligan, J.E. J. Immunol. (2002) [Pubmed]
  12. Mitogen-activated protein kinase activity is involved in effector functions triggered by the CD94/NKG2-C NK receptor specific for HLA-E. Carretero, M., Llano, M., Navarro, F., Bellón, T., López-Botet, M. Eur. J. Immunol. (2000) [Pubmed]
  13. Linkage of the NKG2 and CD94 receptor genes to D12S77 in the human natural killer gene complex. Sobanov, Y., Glienke, J., Brostjan, C., Lehrach, H., Francis, F., Hofer, E. Immunogenetics (1999) [Pubmed]
  14. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. Borrego, F., Ulbrecht, M., Weiss, E.H., Coligan, J.E., Brooks, A.G. J. Exp. Med. (1998) [Pubmed]
  15. A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition. Michaëlsson, J., Teixeira de Matos, C., Achour, A., Lanier, L.L., Kärre, K., Söderström, K. J. Exp. Med. (2002) [Pubmed]
  16. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Gumá, M., Budt, M., Sáez, A., Brckalo, T., Hengel, H., Angulo, A., López-Botet, M. Blood (2006) [Pubmed]
  17. Role that each NKG2A immunoreceptor tyrosine-based inhibitory motif plays in mediating the human CD94/NKG2A inhibitory signal. Kabat, J., Borrego, F., Brooks, A., Coligan, J.E. J. Immunol. (2002) [Pubmed]
  18. Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Chang, C., Rodríguez, A., Carretero, M., López-Botet, M., Phillips, J.H., Lanier, L.L. Eur. J. Immunol. (1995) [Pubmed]
  19. Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway. Zeddou, M., Greimers, R., de Valensart, N., Nayjib, B., Tasken, K., Boniver, J., Moutschen, M., Rahmouni, S. Biochem. Pharmacol. (2005) [Pubmed]
  20. Differentially induced expression of C-type lectins in activated lymphocytes. Eichler, W., Ruschpler, P., Wobus, M., Drössler, K. J. Cell. Biochem. Suppl. (2001) [Pubmed]
  21. HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Llano, M., Lee, N., Navarro, F., García, P., Albar, J.P., Geraghty, D.E., López-Botet, M. Eur. J. Immunol. (1998) [Pubmed]
  22. Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells. Allan, D.S., Colonna, M., Lanier, L.L., Churakova, T.D., Abrams, J.S., Ellis, S.A., McMichael, A.J., Braud, V.M. J. Exp. Med. (1999) [Pubmed]
  23. The CD94/NKG2 C-type lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules. López-Botet, M., Carretero, M., Pérez-Villar, J., Bellón, T., Llano, M., Navarro, F. Immunol. Res. (1997) [Pubmed]
  24. HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. King, A., Allan, D.S., Bowen, M., Powis, S.J., Joseph, S., Verma, S., Hiby, S.E., McMichael, A.J., Loke, Y.W., Braud, V.M. Eur. J. Immunol. (2000) [Pubmed]
  25. The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells. Gumá, M., Busch, L.K., Salazar-Fontana, L.I., Bellosillo, B., Morte, C., García, P., López-Botet, M. Eur. J. Immunol. (2005) [Pubmed]
  26. Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. O'Callaghan, C.A., Bell, J.I. Immunol. Rev. (1998) [Pubmed]
  27. The role of CD94/NKG2 in innate and adaptive immunity. Gunturi, A., Berg, R.E., Forman, J. Immunol. Res. (2004) [Pubmed]
  28. Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset. Barakonyi, A., Rabot, M., Marie-Cardine, A., Aguerre-Girr, M., Polgar, B., Schiavon, V., Bensussan, A., Le Bouteiller, P. J. Immunol. (2004) [Pubmed]
  29. Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2. Miller, J.S., McCullar, V. Blood (2001) [Pubmed]
  30. Cloning of NKG2-F, a new member of the NKG2 family of human natural killer cell receptor genes. Plougastel, B., Trowsdale, J. Eur. J. Immunol. (1997) [Pubmed]
  31. Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I molecules. López-Botet, M., Pérez-Villar, J.J., Carretero, M., Rodríguez, A., Melero, I., Bellón, T., Llano, M., Navarro, F. Immunol. Rev. (1997) [Pubmed]
  32. Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer. Bellón, T., Heredia, A.B., Llano, M., Minguela, A., Rodriguez, A., López-Botet, M., Aparicio, P. J. Immunol. (1999) [Pubmed]
  33. 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. Biassoni, R., Fogli, M., Cantoni, C., Costa, P., Conte, R., Koopman, G., Cafaro, A., Ensoli, B., Moretta, A., Moretta, L., De Maria, A. J. Immunol. (2005) [Pubmed]
  34. Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor. Mingari, M.C., Vitale, C., Cantoni, C., Bellomo, R., Ponte, M., Schiavetti, F., Bertone, S., Moretta, A., Moretta, L. Eur. J. Immunol. (1997) [Pubmed]
  35. Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells. Ding, Y., Sumitran, S., Holgersson, J. Scand. J. Immunol. (1999) [Pubmed]
WikiGenes - Universities