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

• Because 1,2:5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild akali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks [6].

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

• The Tsa-1 locus is located on chromosome 15 linked to Ly6 on the mouse genome [14].
• TSA-1 shares amino acid sequence homology to the mouse Ly6 multigene family, epidermal growth factor-like receptors, and to cobra venom neurotoxin [14].
• The Sca-1 antibody recognizes antigens encoded by members of the Ly-6 multigene family [15].
• The kinetics of the stress-dependent upregulation of Ly-6 expression differed, however, between the epithelial and fibroblastic tumor cells [16].
• Stress conditions such as serum starvation or heat shock upregulated the expression of Ly-6 by the 2 types of tumor cells but did not induce apoptosis in these cells [16].

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

• Monoclonal antibodies to ThB detect close linkage of Ly-6 and a gene regulating ThB expression [25].
• In the present report, we have demonstrated that IFN-gamma also induced Ly-6 molecules on B lymphocytes, several B cell tumors, and bone marrow cells [26].
• The Ly-6 alloantigens have been shown to participate in the process of T cell activation based on the ability of anti-Ly-6 mAb to induce IL-2 production and proliferation of T lymphocytes [27].

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

• Molecular cloning of the cDNA encoding the Ag revealed that this Ag is most likely the human homologue of the murine Ly-6 Ag, ThB [18].
• In Southern blot analysis, the Ly-6.2 cDNA clone detects a multigene family and a restriction fragment length polymorphism that maps precisely to the Ly-6 locus [20].
• To further explore the influence of Ly-6 haplotype on Ly-6A/E expression by specific cell subsets, lymph-node lymphocytes from a panel of mouse strains were analyzed by multiparameter flow cytometry for correlated expression of Ly-6A/E, CD4, and CD8 [30].
• Further dissection of the complexity of the Ly-6 antigen system and determination of its possible functional importance in lymphocyte activation should be greatly facilitated by the availability of xenogeneic mAb that recognize framework determinants on multiple Ly-6 products [31].
• We also evaluated the expression of Ly-6 RNA in cells after treatments with interferons (IFN) and interleukin 1 (IL1) [4].

References