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Gene Review

LY6D  -  lymphocyte antigen 6 complex, locus D

Homo sapiens

Synonyms: E48, E48 antigen, Ly-6D, Lymphocyte antigen 6D
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Disease relevance of LY6D


High impact information on LY6D

  • The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man [5].
  • Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion [5].
  • A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells [5].
  • The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region [5].
  • We have shown phenotypic modulation of tumor cell behavior by E48 expression, including enhanced cell migration in vitro and tumor cell dissemination in vivo [2].

Chemical compound and disease context of LY6D


Biological context of LY6D

  • The functional significance of the E48-mediated up-regulation of Sialyl Lewis a was demonstrated in rolling experiments on E-selectin bearing surfaces under physiological conditions of shear flow and on tumor necrosis factor alpha-activated human umbilical venous endothelial cells [7].
  • Biodistribution and pharmacokinetics of radiolabeled mAb E48 IgG and E48 F(ab')2 were analyzed and compared in 39 patients with histologically proven squamous cell carcinoma of the head and neck who were included in a radioimmunoscintigraphy study and underwent surgery 44 h after injection [8].
  • These data suggest that a specific allosteric binding site on b5, which includes residues E48, E49, and possibly R52, mediates the stimulation of 17,20-lyase activity [9].
  • From the tissue distribution of 800 microCi MAb E48, the absorbed cumulative radiation doses of tumour and various organs were calculated using the trapezoid integration method for the area under the curve [10].
  • Moreover, it was shown that cmAb E48 is highly capable of lysing HNSCC targets in ADCC assays in vitro, whereas the mmAb appeared to be almost inactive [11].

Anatomical context of LY6D

  • Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected [12].
  • The diagnostic value of 99mTc-labeled monoclonal antibody E48 F(ab')2 (750 MBq, 1 mg) was evaluated in 10 patients with a histologically proven squamous cell carcinoma of the head and neck and with clinical evidence of cervical lymph node involvement [13].
  • Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients [14].
  • Tumor uptake of 99mTc-labeled E48 IgG was high, ranging from 0.007 to 0.082% of the injected dose/g, with a mean of 0.031 +/- 0.020% of the injected dose/g. The mean tumor:nontumor ratio of this conjugate was 2.8 for mucosa, 4.6 for bone marrow aspirate, 4.1 for blood, 20.3 for fat, and 21.0 for muscle [8].
  • In cells of normal oral mucosa, the E48 antigen was expressed on the plasmalemma, particularly associated with desmosomes, suggesting involvement of the E48 antigen in intercellular adhesion [15].

Associations of LY6D with chemical compounds

  • Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) microCi 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8) [16].
  • In comparison, injection of 100 micrograms of a MAb E48 coupled to 2 micrograms of fluorescein gave a specific green fluorescence signal in the tumor xenografts, which was detectable, however, only after removing the mouse skin [17].
  • The former cells also expressed higher levels of two major fucosylated glycans (the selectin ligand, Sialyl Lewis a, and VIM-2) than the E48 antisense transfectants [7].
  • Three groups of patients were distinguished: group 1 (n = 19) received technetium-99m (99mTc)-labeled E48 F(ab')2, group 2 (n = 9) received 99mTc-labeled E48 IgG, and group 3 (n = 11) received 99mTc- and 131I-labeled E48 IgG as well as 125I-labeled F(ab')2 [8].
  • The D48E variant possessed an additional residue of gamma-carboxyglutamic acid (Gla), showing that E48 was gamma-carboxylated [18].

Other interactions of LY6D

  • 3. Genes encoding at least two other GPI-anchored molecules, E48 and RIG-E, are also located in this region [19].

Analytical, diagnostic and therapeutic context of LY6D


  1. A gain of novel tissue specificity in the human Ly-6 gene E48. Brakenhoff, R.H., van Dijk, M., Rood-Knippels, E.M., Snow, G.B. J. Immunol. (1997) [Pubmed]
  2. Genetic reprogramming of tumor cells by zinc finger transcription factors. Blancafort, P., Chen, E.I., Gonzalez, B., Bergquist, S., Zijlstra, A., Guthy, D., Brachat, A., Brakenhoff, R.H., Quigley, J.P., Erdmann, D., Barbas, C.F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. A 22-kd surface antigen detected by monoclonal antibody E 48 is exclusively expressed in stratified squamous and transitional epithelia. Quak, J.J., Balm, A.J., van Dongen, G.A., Brakkee, J.G., Scheper, R.J., Snow, G.B., Meijer, C.J. Am. J. Pathol. (1990) [Pubmed]
  4. Use of monoclonal antibody E48 in diagnosing transitional cell carcinoma of urinary bladder. Torenbeek, R., Blomjous, C.E., Quak, J.J., Ybema, S., Meijer, C.J. J. Clin. Pathol. (1992) [Pubmed]
  5. The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion. Brakenhoff, R.H., Gerretsen, M., Knippels, E.M., van Dijk, M., van Essen, H., Weghuis, D.O., Sinke, R.J., Snow, G.B., van Dongen, G.A. J. Cell Biol. (1995) [Pubmed]
  6. Clinical imaging of head and neck cancer with technetium-99m-labeled monoclonal antibody E48 IgG or F(ab')2. de Bree, R., Roos, J.C., Quak, J.J., den Hollander, W., van den Brekel, M.W., van der Wal, J.E., Tobi, H., Snow, G.B., van Dongen, G.A. J. Nucl. Med. (1994) [Pubmed]
  7. The GPI-linked Ly-6 antigen E48 regulates expression levels of the FX enzyme and of E-selectin ligands on head and neck squamous carcinoma cells. Eshel, R., Zanin, A., Sagi-Assif, O., Meshel, T., Smorodinsky, N.I., Dwir, O., Alon, R., Brakenhoff, R., van Dongen, G., Witz, I.P. J. Biol. Chem. (2000) [Pubmed]
  8. Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab')2 in patients with head and neck cancer. de Bree, R., Roos, J.C., Quak, J.J., den Hollander, W., Wilhelm, A.J., van Lingen, A., Snow, G.B., Dongen, G.A. Clin. Cancer Res. (1995) [Pubmed]
  9. Human cytochrome b5 requires residues E48 and E49 to stimulate the 17,20-lyase activity of cytochrome P450c17. Naffin-Olivos, J.L., Auchus, R.J. Biochemistry (2006) [Pubmed]
  10. Radioimmunotherapy of human head and neck squamous cell carcinoma xenografts with 131I-labelled monoclonal antibody E48 IgG. Gerretsen, M., Schrijvers, A.H., van Walsum, M., Braakhuis, B.J., Quak, J.J., Meijer, C.J., Snow, G.B., van Dongen, G.A. Br. J. Cancer (1992) [Pubmed]
  11. Construction and characterization of the chimeric monoclonal antibody E48 for therapy of head and neck cancer. Brakenhoff, R.H., van Gog, F.B., Looney, J.E., van Walsum, M., Snow, G.B., van Dongen, G.A. Cancer Immunol. Immunother. (1995) [Pubmed]
  12. Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma. de Nooij-van Dalen, A.G., van Dongen, G.A., Smeets, S.J., Nieuwenhuis, E.J., Stigter-van Walsum, M., Snow, G.B., Brakenhoff, R.H. Int. J. Cancer (2003) [Pubmed]
  13. Radioimmunoscintigraphy of head and neck cancer using 99mTc-labeled monoclonal antibody E48 F(ab')2. van Dongen, G.A., Leverstein, H., Roos, J.C., Quak, J.J., van den Brekel, M.W., van Lingen, A., Martens, H.J., Castelijns, J.A., Visser, G.W., Meijer, C.J. Cancer Res. (1992) [Pubmed]
  14. Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients. Colnot, D.R., Nieuwenhuis, E.J., Kuik, D.J., Leemans, C.R., Dijkstra, J., Snow, G.B., van Dongen, G.A., Brakenhoff, R.H. Clin. Cancer Res. (2004) [Pubmed]
  15. Evidence for a role of the monoclonal antibody E48 defined antigen in cell-cell adhesion in squamous epithelia and head and neck squamous cell carcinoma. Schrijvers, A.H., Gerretsen, M., Fritz, J.M., van Walsum, M., Quak, J.J., Snow, G.B., van Dongen, G.A. Exp. Cell Res. (1991) [Pubmed]
  16. 186Re-labeled monoclonal antibody E48 immunoglobulin G-mediated therapy of human head and neck squamous cell carcinoma xenografts. Gerretsen, M., Visser, G.W., van Walsum, M., Meijer, C.J., Snow, G.B., van Dongen, G.A. Cancer Res. (1993) [Pubmed]
  17. Antibody-indocyanin conjugates for immunophotodetection of human squamous cell carcinoma in nude mice. Folli, S., Westermann, P., Braichotte, D., Pèlegrin, A., Wagnières, G., van den Bergh, H., Mach, J.P. Cancer Res. (1994) [Pubmed]
  18. Functional consequences of mutations in amino acid residues that stabilize calcium binding to the first epidermal growth factor homology domain of human protein C. Geng, J.P., Cheng, C.H., Castellino, F.J. Thromb. Haemost. (1996) [Pubmed]
  19. Genomic structure and chromosomal localization of GML (GPI-anchored molecule-like protein), a gene induced by p53. Kimura, Y., Furuhata, T., Urano, T., Hirata, K., Nakamura, Y., Tokino, T. Genomics (1997) [Pubmed]
  20. Identification and immunotherapeutic targeting of antigens induced by chemotherapy. Rubinfeld, B., Upadhyay, A., Clark, S.L., Fong, S.E., Smith, V., Koeppen, H., Ross, S., Polakis, P. Nat. Biotechnol. (2006) [Pubmed]
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