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Gene Review

Ly6  -  lymphocyte antigen 6 complex

Mus musculus

Synonyms: Ala-1, DAG, H9/25, Ly-27, Ly-6, ...
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Disease relevance of Ly6

  • Previous work has demonstrated linkage between Ly-6, H-30, and a locus, Ril-1, that affects susceptibility to radiation-induced leukemia [1].
  • Another monoclonal antibody, HD-42, which had been isolated on the basis of its specificity for a fibrosarcoma antigen subsequently found to be Ly-6 related, precipitated the same polypeptides [2].
  • Similar up-regulation of Ly-6 was seen in murine lupus nephritis and in mercuric chloride nephropathy [3].
  • Kinetic analysis of Ly-6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly-6 inducibility in diverse cell types [4].
  • To aid our investigation of these issues, we have constructed a physical map of the entire Ly-6 complex in the C57BL/6 murine genome using the combined techniques of field-inversion gel electrophoresis (FIGE), phage and cosmid genomic library screening, and two-dimensional DNA electrophoresis [5].

Psychiatry related information on Ly6


High impact information on Ly6

  • Treatment of mouse T lymphocytes with antibodies specific for two such proteins, Thy-1 and Ly-6, are known to induce proliferation [7].
  • The mouse Ly6 gene family encodes proteins found in lymphocytes and other cells [8].
  • The Ly-6 locus controls the expression and/or encodes for alloantigenic specificities found primarily on subpopulations of murine T and B lymphocytes [9].
  • This sequence matched that of the recently identified human stem cell antigen, was structurally similar to the mouse Ly-6 gene family, and the sequence predicted it was a glycosyl phosphatidyl inositol (GPI)-anchored protein that had a cleavable COOH-terminal peptide [10].
  • Dianhydrogalactitol (DAG; NSC-132313), a hexitol epoxide, was used to treat intracerebral rodent tumors [11].

Chemical compound and disease context of Ly6

  • Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo on day 9 [12].
  • Liposomes composed of chemically synthesized glyceroglycolipids, such as 1,2-dipalmityl-[beta-cellobiosyl-(1'----3)]- glycerol (Cel-DAG), 1,2-dipalmityl-[beta-lactosyl-(1'----3)]-glycerol, or 1,2-dipalmityl-[beta-maltosyl-(1'----3)]-glycerol, were found to enhance protective immunity against transplantable tumor cells (sarcoma 180) in ICR mice [13].

Biological context of Ly6


Anatomical context of Ly6

  • Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development [14].
  • Rat monoclonal antibodies YE3/19.1, defining the murine-activated lymphocyte antigen MALA-1, and D7, detecting an Ly-6 locus-controlled antigen, bound highly purified Ly-6E [17].
  • These data suggest that the functional elimination of an ancestral Ly-6 exon 1 switched the expression from lymphocytes toward keratinocytes [18].
  • Potential candidate genes for Rfv3 are several genes expressed in cells of the immune system and previously mapped to the same region, including a T-cell antigen gene, Ly6, and three cytokine receptor genes, IL2rb, IL3rb1, and IL3rb2 [19].
  • Expression of the cDNA clone in COS cells demonstrates that it codes for TAP and clarifies the relationship between the epitopes recognized by various alpha Ly-6 monoclonal antibodies [20].

Associations of Ly6 with chemical compounds

  • The translated amino acid sequence has 11 cysteine residues, and together with the absence of potential N-linked glycosylation sites is similar to the structure of the Ly-6 molecules [21].
  • Treatment of whole cell TX-100 lysates or sucrose gradient fractions dotted onto nitrocellulose filter strips with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) proved to be an efficient method to assay for the presence of a GPI-anchor in Thy-1 and Ly6 surface glycoproteins [22].
  • The T-cell-activating protein TAP is a murine phosphatidylinositol-anchored glycoprotein whose expression is controlled by the Ly-6 locus [20].
  • Cyclic AMP response element binding protein and T cell-specific factor-1 (alpha) activities were selectively enhanced by anti-CD3 epsilon, but not by anti-Ly6A/E, which suggests that signaling via the TCR and Ly-6 were not identical [23].
  • Proliferation of thyroid follicular cells is controlled by three intra-cellular cascades [cAMP, inositol 1,4,5-triphosphate (IP3)/Ca2+/diacylglycerol (DAG), and tyrosine kinases] that are activated by distinct extracellular signals and receptors [24].

Regulatory relationships of Ly6


Other interactions of Ly6

  • Mapping of closely linked genes in an interspecific backcross panel allowed us to exclude two previous candidate genes, Ly6 and Wnt7b [28].
  • Electrophoretic analysis showed a similar size and charge for Ly-6A.2, Ly-6B.2, Ly-6D.2, and Ly-27 [17].
  • Analyses of alleles inherited as passengers in B6.C-H-30c, C3H.B-Ly-6b, and C57BL/6By-Eh/+ congenic mouse strains and in situ hybridization experiments support the above gene order and indicate further that the cluster is located on distal chromosome 15, with Ly-6 and Sis near Eh [1].
  • ThB is not expressed on kidney, although some investigators (McKenzie et al. 1977 a, Halloran et al. 1978) report Ly-6 expression on that tissue [25].
  • As a result of this Taq I RFLP, a cross between Mus musculus domesticus and BALB/cJ permitted the positioning of Myc-1 on chromosome 15 with respect to Ly-6, Sis, and Gdc-1 [29].

Analytical, diagnostic and therapeutic context of Ly6


  1. Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 --Gdc-1 region to mouse chromosome 15. Meruelo, D., Rossomando, A., Scandalis, S., D'Eustachio, P., Fournier, R.E., Roop, D.R., Saxe, D., Blatt, C., Nesbitt, M.N. Immunogenetics (1987) [Pubmed]
  2. Biochemical characterization of the murine activated lymphocyte alloantigen Ly-6E.1 controlled by the Ly-6 locus. Palfree, R.G., Hämmerling, U. J. Immunol. (1986) [Pubmed]
  3. Ly-6 in kidney is widely expressed on tubular epithelium and vascular endothelium and is up-regulated by interferon gamma. Blake, P.G., Madrenas, J., Halloran, P.F. J. Am. Soc. Nephrol. (1993) [Pubmed]
  4. Kinetic analysis of Ly-6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly-6 inducibility in diverse cell types. LeClair, K.P., Bridgett, M.M., Dumont, F.J., Palfree, R.G., Hämmerling, U., Bothwell, A.L. Eur. J. Immunol. (1989) [Pubmed]
  5. Long-range physical map of the Ly-6 complex: mapping the Ly-6 multigene family by field-inversion and two-dimensional gel electrophoresis. Kamiura, S., Nolan, C.M., Meruelo, D. Genomics (1992) [Pubmed]
  6. Phase I study of a five-day intermittent schedule for 1,2:5,6-dianhydrogalactitol (NSC-132313). Eagan, R.T., Moertel, C.G., Hahn, R.G., Schutt, A.J. J. Natl. Cancer Inst. (1976) [Pubmed]
  7. A glycophospholipid anchor is required for Qa-2-mediated T cell activation. Robinson, P.J., Millrain, M., Antoniou, J., Simpson, E., Mellor, A.L. Nature (1989) [Pubmed]
  8. Ly6d-L, a cell surface ligand for mouse Ly6d. Apostolopoulos, J., McKenzie, I.F., Sandrin, M.S. Immunity (2000) [Pubmed]
  9. Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies. Malek, T.R., Ortega, G., Chan, C., Kroczek, R.A., Shevach, E.M. J. Exp. Med. (1986) [Pubmed]
  10. Cloning and identification of human Sca as a novel inhibitor of osteoclast formation and bone resorption. Choi, S.J., Devlin, R.D., Menaa, C., Chung, H., Roodman, G.D., Reddy, S.V. J. Clin. Invest. (1998) [Pubmed]
  11. Dianhydrogalactitol (NSC-132313): pharmacokinetics in normal and tumor-bearing rat brain and antitumor activity against three intracerebral rodent tumors. Levin, V.A., Freeman-Dove, M.A., Maroten, C.E. J. Natl. Cancer Inst. (1976) [Pubmed]
  12. Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy. Hiramatsu, Y., Sekiguchi, N., Hayashi, M., Isshiki, K., Yokota, T., King, G.L., Loeken, M.R. Diabetes (2002) [Pubmed]
  13. Activation of mouse peritoneal macrophages by synthetic glyceroglycolipid liposomes. Naito, M., Kudo, I., Mukai-Sato, Y., Tsushima, S., Nomura, H., Nojima, S., Inoue, K. Cancer Immunol. Immunother. (1987) [Pubmed]
  14. Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development. MacNeil, I., Kennedy, J., Godfrey, D.I., Jenkins, N.A., Masciantonio, M., Mineo, C., Gilbert, D.J., Copeland, N.G., Boyd, R.L., Zlotnik, A. J. Immunol. (1993) [Pubmed]
  15. Cloning of the complete Ly-6E.1 gene and identification of DNase I hypersensitive sites corresponding to expression in hematopoietic cells. Sinclair, A.M., Dzierzak, E.A. Blood (1993) [Pubmed]
  16. Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress. Treister, A., Sagi-Assif, O., Meer, M., Smorodinsky, N.I., Anavi, R., Golan, I., Meshel, T., Kahana, O., Eshel, R., Katz, B.Z., Shevach, E., Witz, I.P. Int. J. Cancer (1998) [Pubmed]
  17. Ly-6A.2 and Ly-6E.1 molecules are antithetical and identical to MALA-1. Palfree, R.G., Dumont, F.J., Hammerling, U. Immunogenetics (1986) [Pubmed]
  18. 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]
  19. Chromosome mapping of Rfv3, a host resistance gene to Friend murine retrovirus. Hasenkrug, K.J., Valenzuela, A., Letts, V.A., Nishio, J., Chesebro, B., Frankel, W.N. J. Virol. (1995) [Pubmed]
  20. Cloning and expression of a cDNA for the T-cell-activating protein TAP. Reiser, H., Coligan, J., Palmer, E., Benacerraf, B., Rock, K.L. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  21. Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB). Gumley, T.P., McKenzie, I.F., Kozak, C.A., Sandrin, M.S. J. Immunol. (1992) [Pubmed]
  22. Evaluation by dot-immunoassay of the differential distribution of cell surface and intracellular proteins in glycosylphosphatidylinositol-rich plasma membrane domains. Ilangumaran, S., Arni, S., Chicheportiche, Y., Briol, A., Hoessli, D.C. Anal. Biochem. (1996) [Pubmed]
  23. Regulation of nuclear factor-kappa B and activator protein-1 activities after stimulation of T cells via glycosylphosphatidylinositol-anchored Ly-6A/E. Ivanov, V., Fleming, T.J., Malek, T.R. J. Immunol. (1994) [Pubmed]
  24. Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells. Ledent, C., Denef, J.F., Cottecchia, S., Lefkowitz, R., Dumont, J., Vassart, G., Parmentier, M. Endocrinology (1997) [Pubmed]
  25. Monoclonal antibodies to ThB detect close linkage of Ly-6 and a gene regulating ThB expression. Eckhardt, L.A., Herzenberg, L.A. Immunogenetics (1980) [Pubmed]
  26. Tumor necrosis factor synergistically acts with IFN-gamma to regulate Ly-6A/E expression in T lymphocytes, thymocytes and bone marrow cells. Malek, T.R., Danis, K.M., Codias, E.K. J. Immunol. (1989) [Pubmed]
  27. Activation of T lymphocytes through the Ly-6 pathway is defective in A strain mice. Malek, T.R., Shevach, E.M., Danis, K.M. J. Immunol. (1989) [Pubmed]
  28. Fine mapping of the friend retrovirus resistance gene, Rfv3, on mouse chromosome 15. Super, H.J., Hasenkrug, K.J., Simmons, S., Brooks, D.M., Konzek, R., Sarge, K.D., Morimoto, R.I., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Frankel, W., Chesebro, B. J. Virol. (1999) [Pubmed]
  29. Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15. Huppi, K., Duncan, R., Potter, M. Immunogenetics (1988) [Pubmed]
  30. Mouse strain variability in the expression of the hematopoietic stem cell antigen Ly-6A/E by bone marrow cells. Spangrude, G.J., Brooks, D.M. Blood (1993) [Pubmed]
  31. Role of Ly-6 in lymphocyte activation. I. Characterization of a monoclonal antibody to a nonpolymorphic Ly-6 specificity. Ortega, G., Korty, P.E., Shevach, E.M., Malek, T.R. J. Immunol. (1986) [Pubmed]
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