Disease relevance of LY75

• Hodgkin's lymphoma cell lines express a fusion protein encoded by intergenically spliced mRNA for the multilectin receptor DEC-205 (CD205) and a novel C-type lectin receptor DCL-1 [1].
• These results suggest that analysis of gp200-MR6 expression may be useful in tumour grading and prognostic evaluation in breast cancer [2].
• Furthermore, a preliminary study showed that benign epithelial hyperplasia of the breast expresses the gp200-MR6 heterogeneously [2].
• Bladder carcinomas and normal urothelium universally express gp200-MR6, a molecule functionally associated with the interleukin 4 receptor (CD 124) [3].
• In order to generate reagents that could be used in murine thymic functional studies we isolated antibodies specific to human gp200-MR6, using a phage display library expressing single-chain (sFv) antibodies [4].

High impact information on LY75

• Immature (DEC205, CD1a) and activated/mature (CD83, CD40) dendritic cell transcripts were significantly elevated in ALS tissues [5].
• Notably, qualitatively different immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule expressed on CD8alpha+CD4-CD11b- DCs, dermal DCs, and Langerhans cells [6].
• Those expressing CD8alpha together with CD205, found primarily in the T-cell areas of the spleen and lymph nodes, are the major subset responsible for cross-presenting cellular antigens [7].
• The resulting reading frames encode the DEC-205 ectodomain plus the DCL-1 ectodomain, the transmembrane, and the cytoplasmic domain [1].
• Using 3'-rapid amplification of cDNA ends (RACE) we identified an alternative mRNA for the DEC-205 multilectin receptor in the HRS cell line L428 [1].

Biological context of LY75

• The DEC-205 and DCL-1 genes comprising 35 and 6 exons, respectively, are juxtaposed on chromosome band 2q24 and separated by only 5.4 kb [1].
• The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family [8].
• Strong amino acid sequence identity (77%) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role [8].
• We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes [8].
• Moreover, the molecule may be involved early in the process of tumorigenesis of the breast, in which a loss or a down-regulation of gp200-MR6 could contribute towards tumour development and progression via an effect on cell growth and differentiation [2].

Anatomical context of LY75

• The RT-PCR analysis detected low levels of DEC-205 mRNA in immature blood DC, Langerhans cells (LC) and immature monocyte-derived DC (Mo-DC) [9].
• The universal expression of gp200-MR6 in neoplastic and non-neoplastic urothelium has important implications for the possible use of IL-4 in tumour therapy and suggests that IL- 4 may play a role in differentiation and homeostasis of urothelium and other mucosal epithelia [3].
• cDNA cloning of human DEC-205, a putative antigen-uptake receptor on dendritic cells [10].
• In tissue sections, MG38 identified DEC-205 on thymic cortical epithelium and DCs in the thymic medulla and tonsillar T cell areas [11].
• A hybridoma, MG38, which specifically recognized the immunogen was obtained from a DEC-205 knockout mouse [11].

Associations of LY75 with chemical compounds

• Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules [8].
• We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure [8].
• Monoclonal antibody (mAb) MR6 recognises a 200 kDa glycoprotein, gp200-MR6, which is expressed at high levels on the surface of human thymic cortical epithelium [12].

Regulatory relationships of LY75

• In addition, CRP dramatically down-regulated expression of the antigen-uptake molecules CD205 and CD206, resulting in reduced DC endocytosis [13].

Other interactions of LY75

• Monoclonal antibody MR6 detects gp200-MR6, a molecule functionally associated with the interleukin 4 (IL- 4) receptor [3].
• In addition we demonstrate in both naive Lewis rats and C57BL/6 mice the presence of increased numbers of cells bearing DC markers (OX62 and MHCII, in rats, or CD11C, 33D1, MHCII, and F4/80, but not DEC205, in mice) in sites of brain delivery of RAdhsFlt3L [14].
• Emphasis was laid on expression patterns of DEC-205/CD205 and BDCA-2, a marker for plasmacytoid dendritic cells [15].
• In addition, 3 DC maturation markers not present on the microarrays (DEC205, DC LAMP and CCR7) were analyzed using real-time RT-PCR and found to be up-regulated at several time points [16].
• This review discusses the structure and function of these four proteins-the mannose receptor (MR), the M-type receptor for secretory phospholipases A(2) (PLA(2)R), DEC-205/gp200-MR6 and Endo180/uPARAP [17].

Analytical, diagnostic and therapeutic context of LY75

• Sequence analysis revealed that the mRNA encodes a fusion protein between DEC-205 and a novel C-type lectin DCL-1 [1].
• Northern blot analysis detected 7.8 and 9.5 kilobase DEC-205 transcripts in myeloid, B lymphoid, and Hodgkin's disease-derived cell lines [10].
• The DEC-205 gene (LY75) was mapped to chromosome band 2q24 by somatic cell hybrid panel analysis and fluorescent in situ hybridization [10].
• As opposed to the uniform absence of donor LC at the time of transplantation, examination of the epidermis from the grafts after 2-4 weeks revealed MHC class II(+) donor cells, which had acquired CD205 and CD207, thus qualifying them as LC [18].

References