Recombinant Human LAG-3 Protein (C-Fc)

Name: Recombinant Human LAG-3 Protein (C-Fc)
Brand: Beta LifeScience
SKU: BL-0188NP
Availability: InStock

BL-0188NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: All products, Co-inhibitory receptors, Featured immune checkpoint protein molecules, High-quality recombinant proteins, Immune checkpoint proteins

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Product Overview

Description	Recombinant Human Lymphocyte Activation Gene 3 Protein is produced by our Mammalian expression system and the target gene encoding Leu23-Leu450 is expressed with a human IgG1 Fc tag at the C-terminus.
Accession	P18627
Synonym	Lymphocyte activation gene 3 protein;LAG3;LAG-3;Protein FDC;CD223
Gene Background	Human Lymphocyte activation gene 3 protein( LAG3) is a member of immunoglobulin (Ig) superfamily. LAG3 contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. LAG3 is involved in lymphocyte activation and can bind to HLA class-II antigens. It is selectively expressed in activated T and NK cells. LAG3 has a negative regulatory function in T cells and acts as as a new marker of T cell induced B cell activation. As a soluble molecule, LAG3 activates antigen-presenting cells through MHC class II signaling. It can lead to increased antigen-specific T-cell responses in vivo. LAG-3 has higher affinity to MHC class II than CD4.
Molecular Mass	73.3 KDa
Apmol Mass	70-90 KDa, reducing conditions
Formulation	Supplied as a 0.2 μm filtered solution of 20mM NaH2PO4, 150mM NaCl, 0.1M Arginine, 0.1M Glu, 10% Glycerol, 0.01% Tween20, 5% Trehalose, pH 7.4.
Endotoxin	Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity	Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Biologically active. Please contact us to obtain bioactivity data.
Reconstitution
Storage	Store at ≤-70°C, stable for 6 months after receipt. Store at ≤-70°C, stable for 3 months under sterile conditions after opening. Please minimize freeze-thaw cycles.
Shipping	The product is shipped on dry ice/polar packs. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells. Delivers inhibitory signals upon binding to ligands, such as FGL1. FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function. Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1. Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells. Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function. Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation. Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear.; May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response.
Subcellular Location	[Lymphocyte activation gene 3 protein]: Cell membrane; Single-pass type I membrane protein.; [Secreted lymphocyte activation gene 3 protein]: Secreted.
Database References	HGNC: 6476 OMIM: 153337 KEGG: hsa:3902 STRING: 9606.ENSP00000203629 UniGene: PMID: 30272332 These results together suggested that LAG-3 is a marker of CD4(+) T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells. PMID: 29671649 Among the 89 patients, CD274, LAG3, and IDO1 expressions in TIICs were observed in 68.6% (61 cases), 13.5% (12), and 28.1% (25) of patients, respectively. CD274, CTLA4, and IDO1 were expressed in tumor cells of 24.7% (22 cases), 4.5% (4), and 72.0% (64) of patients, respectively. PMID: 29520442 LAG-3+ iTILs are enriched in estrogen receptor-negative breast cancers and represent an independent favorable prognostic factor. In addition, a high proportion of PD-1/PD-L1+ tumors are co-infiltrated with LAG-3+ TILs. PMID: 29045526 Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibitory receptors. PMID: 27835902 Data suggest that blocking LAG3-MHC class II interactions is a potential therapeutic target in chronic lymphocytic leukemia. PMID: 28154084 LAG-3 expression was correlated with expression of PD-1 on TILs and expression of PD-L1 on tumor cells. Higher expression of LAG-3 on TILs was significantly correlated with higher expression of PD-1 on TILs and higher expression of PD-L1 on tumor cells. PMID: 28132868 the upregulation of others syncytial molecules, including LAG3, CTLA4, CD28 and CD3, assisting the formation of syncytia with APC cells. PMID: 27108398 LAG3-expressing CD4(+)CD25(-) T cells represent another regulatory immune cell type with potential to interfere with anti-tumor immunity. PMID: 28935468 Overexpression of lymphocyte activation gene-3 inhibits regulatory T cell responses in osteoarthritis PMID: 28800255 Egr2-driven cell surface proteins LAG-3 and 4-1BB can identify dysfunctional tumor antigen-specific CD8(+) TIL. PMID: 28115575 our data indicate that the evaluation of stromal TILs remains the most reliable immune prognostic marker in TNBC, and support the clinical evaluation of anti-PD-1/PD-L1 and anti-LAG-3 in a subset of patients with TNBC who have concurrent expression of both checkpoint receptors. PMID: 27912781 this review provides the translational rationale for targeting LAG3, as well as historical and current state of clinical trials utilizing LAG3 cancer immunomodulators PMID: 28258692 this study shows that LAG3 expressed on myeloid leukaemia cells possess the capacity to facilitate functional exhaustion in T helper cells PMID: 27565576 epigenetic modification on LAG-3 increased LAG-3(+) T cells and its immune regulatory roles in chronic osteomyelitis progression PMID: 28028751 Immune checkpoint proteins are co-inhibitory factors that can diminish the antigen-specific immune responses by attenuating the regulatory role of cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1, lymphocyte-activation gene 3, and T-cell immunoglobulin mucin-3. PMID: 28349816 LAG3 binds alpha-synuclein preformed fibrils (PFF) with high affinity (dissociation constant = 77 nanomolar), whereas the alpha-syn monomer exhibited minimal binding. alpha-Syn-biotin PFF binding to LAG3 initiated alpha-syn PFF endocytosis, transmission, and toxicity. PMID: 27708076 An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy. PMID: 26013006 LAG-3 is highly expressed in peripheral blood CD8+ T cells in chronic HBV-infected patients. PMID: 27053622 iNKT cytokine production is profoundly altered by both HIV infection and treatment, and LAG-3, but not PD-1, expression is associated with a reduction in iNKT IFNgamma production. PMID: 25810006 NFKB1, CD27, LAG3 and IKZF3 are new susceptibility genes for psoriasis. PMID: 25006012 The elevated expression of LAG-3 at the genital tract suggests it may regulate T-cell activation, and identify cells susceptible to HIV infection. The enrichment of LAG-3 on double negative T cells suggests LAG-3 may contribute to the immunoregulatory activity of these cells. PMID: 25154740 the LAG-3/MHC class II pathway may synergize with PD-1/PD ligand to enhance T cell-mediated immune responses. PMID: 25780040 LAG-3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells. PMID: 25108024 These results suggest that LAG-3-mediated activation of plasmacytoid dendritic cells takes place in vivo at tumor sites, and it is in part responsible for directing an immune-suppressive environment. PMID: 24441096 Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients. PMID: 23261718 our data suggest that the LAG-3-MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma PMID: 21441454 Multiple myeloma was associated with 2 SNPs in intron regions of LAG3 within 20 k base pairs 5' upstream of the candidate CD4 gene. The variant in LAG3 gene itself may play a role in susceptibility of MM. PMID: 20568250 Analysis identified a gene-set (LAG3, LPL, ZAP70) whose overexpression is assigned to unmutated immunoglobulin variable heavy chain region with 90% specificity. PMID: 20228263 LAG-3 defines an active CD4(+)CD25(high)Foxp3(+) regulatory T cell subset whose frequency is enhanced in the PBMCs of patients with cancer PMID: 20421648 Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. PMID: 20385810 MHC class II-mediated signals induced by the natural ligand, LAG-3, lead to complete maturation of monocyte-derived dendritic cells, which acquire the capacity to trigger naive T cells and drive polarized Th1 responses. PMID: 11937541 LAG-3 induces rapid protein phosphorylation of phospholipase Cgamma2 and p72syk as well as activation of phosphatidyl inositol 3-kinase/Akt, p42/44 extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways. PMID: 12775570 LAG3 may mediate sphingolipid metabolism PMID: 12825348 LAG-3 activates antigen-presenting cells through MHC class II signalling, leading to increased antigen-specific T-cell responses in vivo. PMID: 14644131 regulatory T cells and LAG-3 have pivotal roles in the suppression of EBV-specific cell-mediated immunity in Hodgkin lymphoma PMID: 16757686 The result, including a total of 2640 MS patients and 2194 controls shows no significant association with CD4 and LAG3 and MS. We conclude that these genes are of minor importance in regard of genetic predisposition to the MS. PMID: 17020785 Soluble human recombinant fusion protein (hLAG-3Ig) used in vitro as a single maturation agent induces phenotypic maturation of monocyte-derived dendritic cells and promotes the production of chemokines and TNF-alpha inflammatory cytokine. PMID: 18322184

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

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