Alternative titles; symbols
HGNC Approved Gene Symbol: LY75
Cytogenetic location: 2q24.2 Genomic coordinates (GRCh38) : 2:159,803,355-159,904,756 (from NCBI)
Dendritic cells (DC) are highly effective antigen-presenting cells, capturing antigens through pinocytosis or receptor-mediated endocytosis, processing the antigens, and then loading the antigens onto MHC molecules for presentation to T cells. These processes drive migration and maturation of DC. Jiang et al. (1995) proposed that mouse Dec205, which has a marked similarity to the macrophage mannose receptor (MRC1; 153618), is involved in endocytosis of antigen on dendritic cells. By RT-PCR with degenerate primers based on the sequence of mouse Dec205, followed by 3-prime RACE using a DC-like cell line, Kato et al. (1998) cloned a cDNA for the human homolog of Dec205, designated lymphocyte antigen-75 (LY75) by the HUGO Nomenclature Committee. The complete cDNA for LY75 encodes a 1,722-amino acid protein with a molecular mass of 198 kD. The LY75 protein has 77% overall amino acid identity with mouse Dec205. LY75 is a member of the MMR family of multidomain molecules. It contains a signal peptide, a cysteine-rich domain, a fibronectin type II domain, 10 carbohydrate recognition-like domains, a transmembrane domain, and a cytoplasmic tail. Northern blot analysis of hematopoietic cell lines revealed the presence of a predominant 7.8-kb and a secondary 9.5-kb transcript in myeloid, B-cell, and Hodgkin cell lines but not in the Jurkat T-cell line. In peripheral blood, immature DC contained barely detectable transcripts, which increased 50-fold upon differentiation and activation.
McKay et al. (1998) observed that a molecule that they termed GP200-MR6 appeared to have both promaturational as well as antiproliferative actions on B lymphocytes. They cloned GP200-MR6, which is identical to LY75. Northern blot analysis revealed expression in spleen, thymus, colon, and peripheral blood lymphocytes and low or negative expression in small intestine, prostate, testis, and ovary. The protein appeared to intercept IL4-mediated growth/maturation systems, possibly mediated by its tyrosine kinase activity.
DEC205/DCL1 Fusion Protein
By 3-prime RACE analysis of DEC205 in a Hodgkin and Reed-Sternberg (HRS) lymphoma cell line, Kato et al. (2003) identified a cDNA encoding a fusion of DEC205 with DCL1 (CD302; 612246). Northern blot analysis showed that the 9.5-kb DEC205/DCL1 fusion mRNA was predominately expressed in HRS cell lines. RT-PCR revealed that HRS cells expressed at least 2 variant DEC205/DCL1 mRNAs, one with DEC205 exon 34 fused to DCL1 exon 2, and the other with DEC205 exon 33 fused to DCL1 exon 2. The fusion variants appeared to be generated by cotranscription of both DEC205 and DCL1, followed by intergenic splicing to remove DEC205 exon 35 alone or both exons 34 and 35 along with DCL1 exon 1. The resulting ORFs encode all or most of the DEC205 ectodomain plus the DCL1 ectodomain, transmembrane domain, and cytoplasmic domain. Immunoprecipitation and Western blot analysis showed that the fusion mRNA was translated into a 180-kD DEC205/DCL1 fusion protein in HRS cell lines.
Kato et al. (2003) determined that the DEC205 gene contains 35 exons.
By somatic cell hybrid analysis and FISH, Kato et al. (1998) mapped the LY75 gene to chromosome 2q24. By genomic sequence analysis, Kato et al. (2003) determined that the LY75 gene is located approximately 5.4 kb upstream of the DCL1 gene.
Jiang, W., Swiggard, W. J., Heufler, C., Peng, M., Mirza, A., Steinman, R. M., Nussenzweig, M. C. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375: 151-155, 1995. [PubMed: 7753172] [Full Text: https://doi.org/10.1038/375151a0]
Kato, M., Khan, S., Gonzalez, N., O'Neill, B. P., McDonald, K. J., Cooper, B. J., Angel, N. Z., Hart, D. N. J. 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. J. Biol. Chem. 278: 34035-34041, 2003. [PubMed: 12824192] [Full Text: https://doi.org/10.1074/jbc.M303112200]
Kato, M., Neil, T. K., Clark, G. J., Morris, C. M., Sorg, R. V., Hart, D. N. J. cDNA cloning of human DEC-205, a putative antigen-uptake receptor on dendritic cells. Immunogenetics 47: 442-450, 1998. [PubMed: 9553150] [Full Text: https://doi.org/10.1007/s002510050381]
McKay, P. F., Imami, N., Johns, M., Taylor-Fishwick, D. A., Sedibane, L. M., Totty, N. F., Hsuan, J. J., Palmer, D. B., George, A. J. T., Foxwell, B. M. J., Ritter, M. A. 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. Europ. J. Immun. 28: 4071-4083, 1998. [PubMed: 9862343] [Full Text: https://doi.org/10.1002/(SICI)1521-4141(199812)28:12<4071::AID-IMMU4071>3.0.CO;2-O]