LY75

Official Full Name

lymphocyte antigen 75

Organism

Homo sapiens

GeneID

4065

Background

Predicted to enable signaling receptor activity. Predicted to be involved in immune response and inflammatory response. Located in extracellular exosome. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

CD205; LY-75; CLEC13B; DEC-205; GP200-MR6;

Bio Chemical Class

C-type lectin

Protein Sequence

MRTGWATPRRPAGLLMLLFWFFDLAEPSGRAANDPFTIVHGNTGKCIKPVYGWIVADDCDETEDKLWKWVSQHRLFHLHSQKCLGLDITKSVNELRMFSCDSSAMLWWKCEHHSLYGAARYRLALKDGHGTAISNASDVWKKGGSEESLCDQPYHEIYTRDGNSYGRPCEFPFLIDGTWHHDCILDEDHSGPWCATTLNYEYDRKWGICLKPENGCEDNWEKNEQFGSCYQFNTQTALSWKEAYVSCQNQGADLLSINSAAELTYLKEKEGIAKIFWIGLNQLYSARGWEWSDHKPLNFLNWDPDRPSAPTIGGSSCARMDAESGLWQSFSCEAQLPYVCRKPLNNTVELTDVWTYSDTRCDAGWLPNNGFCYLLVNESNSWDKAHAKCKAFSSDLISIHSLADVEVVVTKLHNEDIKEEVWIGLKNINIPTLFQWSDGTEVTLTYWDENEPNVPYNKTPNCVSYLGELGQWKVQSCEEKLKYVCKRKGEKLNDASSDKMCPPDEGWKRHGETCYKIYEDEVPFGTNCNLTITSRFEQEYLNDLMKKYDKSLRKYFWTGLRDVDSCGEYNWATVGGRRRAVTFSNWNFLEPASPGGCVAMSTGKSVGKWEVKDCRSFKALSICKKMSGPLGPEEASPKPDDPCPEGWQSFPASLSCYKVFHAERIVRKRNWEEAERFCQALGAHLSSFSHVDEIKEFLHFLTDQFSGQHWLWIGLNKRSPDLQGSWQWSDRTPVSTIIMPNEFQQDYDIRDCAAVKVFHRPWRRGWHFYDDREFIYLRPFACDTKLEWVCQIPKGRTPKTPDWYNPDRAGIHGPPLIIEGSEYWFVADLHLNYEEAVLYCASNHSFLATITSFVGLKAIKNKIANISGDGQKWWIRISEWPIDDHFTYSRYPWHRFPVTFGEECLYMSAKTWLIDLGKPTDCSTKLPFICEKYNVSSLEKYSPDSAAKVQCSEQWIPFQNKCFLKIKPVSLTFSQASDTCHSYGGTLPSVLSQIEQDFITSLLPDMEATLWIGLRWTAYEKINKWTDNRELTYSNFHPLLVSGRLRIPENFFEEESRYHCALILNLQKSPFTGTWNFTSCSERHFVSLCQKYSEVKSRQTLQNASETVKYLNNLYKIIPKTLTWHSAKRECLKSNMQLVSITDPYQQAFLSVQALLHNSSLWIGLFSQDDELNFGWSDGKRLHFSRWAETNGQLEDCVVLDTDGFWKTVDCNDNQPGAICYYSGNETEKEVKPVDSVKCPSPVLNTPWIPFQNCCYNFIITKNRHMATTQDEVHTKCQKLNPKSHILSIRDEKENNFVLEQLLYFNYMASWVMLGITYRNKSLMWFDKTPLSYTHWRAGRPTIKNEKFLAGLSTDGFWDIQTFKVIEEAVYFHQHSILACKIEMVDYKEEYNTTLPQFMPYEDGIYSVIQKKVTWYEALNMCSQSGGHLASVHNQNGQLFLEDIVKRDGFPLWVGLSSHDGSESSFEWSDGSTFDYIPWKGQTSPGNCVLLDPKGTWKHEKCNSVKDGAICYKPTKSKKLSRLTYSSRCPAAKENGSRWIQYKGHCYKSDQALHSFSEAKKLCSKHDHSATIVSIKDEDENKFVSRLMRENNNITMRVWLGLSQHSVDQSWSWLDGSEVTFVKWENKSKSGVGRCSMLIASNETWKKVECEHGFGRVVCKVPLGPDYTAIAIIVATLSILVLMGGLIWFLFQRHRLHLAGFSSVRYAQGVNEDEIMLPSFHD

Open

Disease

Breast cancer

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

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Detailed Information

LY75 (Lymphocyte Antigen 75), also known as CD205 or DEC-205, is encoded by a gene located on chromosome 2q24.2. It is a type I transmembrane glycoprotein belonging to the C-type lectin receptor family and is widely involved in immune processes such as antigen uptake, processing, and presentation. It is expressed in dendritic cells (DCs), thymic cortical epithelial cells, B cells, and T cells, playing a key role in antigen presentation and immune response initiation.

Molecular Structure and Functional Characteristics

CD205 consists of an N-terminal cysteine-rich domain (CyR), a fibronectin type II domain (FnII), and ten C-type lectin-like domains (CTLDs). Although these domains are structurally similar to C-type lectins, they lack traditional carbohydrate-binding functions. Its short cytoplasmic tail contains functional endocytic motifs that enable clathrin-mediated endocytosis to transport bound antigens to endosomes, which subsequently bind to major histocompatibility complex (MHC) molecules for antigen presentation.

Additionally, CD205 plays an important role in antigen cross-presentation, capable of presenting exogenous antigens to CD8+ T cells to stimulate cytotoxic immune responses. It also has inhibitory effects on B-cell proliferation.

Tissue Expression and Physiological Functions

CD205 is primarily expressed in immune-related tissues, including the spleen, thymus, colon, and peripheral blood lymphocytes. Its expression is particularly abundant in dendritic cells, where it participates in antigen uptake and presentation processes. Moreover, CD205 is expressed in certain epithelial cells, macrophages, and B cells, demonstrating its functional diversity across various cell types.

Figure 1: Schematic representation of CpG-induced signaling pathways in B cells. Figure 1. CD205 (DEC-205) facilitates the uptake and delivery of CpG to endosomal TLR9, initiating downstream signaling cascades.

In immune responses, CD205 mediates antigen endocytosis and presentation, promoting T cell activation and proliferation, thereby initiating adaptive immune responses. It also plays important roles in maintaining immune tolerance and regulating autoimmune responses.

Expression and Function in Tumors

Research indicates that CD205 is abnormally expressed in various tumors, particularly showing significantly elevated levels in high-grade serous ovarian cancer (HGSC). CD205 overexpression is closely associated with epithelial-mesenchymal transition (EMT) in tumor cells, promoting tumor cell migration and invasion. In ovarian cancer cell lines, inhibiting LY75 expression can induce mesenchymal-epithelial transition (MET), reducing cell migration and invasion capabilities, suggesting that CD205 plays a crucial role in tumor progression and metastasis.

Furthermore, CD205 also exhibits high expression in solid tumors such as gastric cancer, lung cancer, bladder cancer, and triple-negative breast cancer, indicating its potential as a therapeutic target across multiple tumor types.

Potential as an Antibody-Drug Conjugate (ADC) Target

CD205's high expression and rapid internalization properties make it an ideal target for antibody-drug conjugate (ADC) therapy. MEN1309/OBT076 is a CD205-targeting ADC composed of a humanized IgG1 antibody linked to the microtubule inhibitor DM4 via a cleavable linker. In various lymphoma cell lines, MEN1309/OBT076 demonstrates potent antitumor activity with half-inhibitory concentrations (IC50) at nanomolar levels, strongly correlating with CD205 expression levels.

In in vivo experiments, MEN1309/OBT076 shows significant antitumor effects in diffuse large B-cell lymphoma (DLBCL) models, achieving complete remission with a single dose and demonstrating synergistic effects when combined with BCL2 inhibitor venetoclax and anti-CD20 monoclonal antibody rituximab.

Research on CD205 as an ADC target is still in the preclinical stage, but studies have shown promising therapeutic potential in various tumor models. Currently, MEN1309/OBT076 is undergoing early clinical trials to evaluate its safety and efficacy in patients with solid tumors and lymphomas.

Additionally, CD205's role in immune regulation has garnered widespread attention. Its functions in regulating dendritic cell maturation, T cell activation, and maintaining immune tolerance make it a potential target for cancer immunotherapy and vaccine development.

As a multifunctional endocytic receptor, CD205 plays important roles in immune responses, antigen presentation, and tumor progression. Its high expression in various tumors and rapid internalization properties make it a promising target for ADC therapy. In the future, with deeper research into CD205's functional mechanisms, more CD205-based targeted therapeutic strategies may be developed, offering new treatment options for cancer patients.

References

Magatti M, Masserdotti A, Bonassi Signoroni P, et al. B Lymphocytes as Targets of the Immunomodulatory Properties of Human Amniotic Mesenchymal Stromal Cells. Front Immunol. 2020;11:1156.
Gil M, Kim KE. Systematic Multiomic Analysis of Ly75 Gene Expression and Its Prognostic Value Through the Infiltration of Natural Killer (NK) Cells in Skin Cutaneous Melanoma. J Clin Med. 2020 May 8;9(5):1383.

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