Recombinant Mouse CTLA-4 Protein (C-6His)

Name: Recombinant Mouse CTLA-4 Protein (C-6His)
Brand: Beta LifeScience
SKU: BL-0321NP
Availability: InStock

BL-0321NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: Antibody / cell therapy targets, Antibody therapeutic / adc target proteins, Co-inhibitory receptors, Featured immune checkpoint protein molecules, High-quality recombinant proteins, Immune checkpoint proteins

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Product Overview

Description	Recombinant Mouse Cytotoxic T-lymphocyte Protein 4 is produced by our Mammalian expression system and the target gene encoding Ala37-Asp161 is expressed with a 6His tag at the C-terminus.
Accession	P09793
Synonym	Cytotoxic T-lymphocyte protein 4; Cytotoxic T-lymphocyte-associated antigen 4; CTLA-4; CD152; Ctla4
Gene Background	Mouse Cytotoxic Tlymphocyte 4(CTLA-4,CD152), is a type I transmembrane T cell inhibitory molecule. mouse CTLA4 cDNA encodes 223 amino acids (aa) including a 35 aa signal sequence, a 126 aa extracellular domain (ECD) with one Ig-like V-type domain, a 21 aa transmembrane (TM) sequence, and a 41 aa cytoplasmic sequence. Within the ECD, Mouse CTLA-4 shares 68% aa sequence identity with human. CTLA4 is similar to the T cell costimulatory protein CD28 since both of the molecules bind to CD80 and CD86 on antigen-presenting cells. CTLA4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal. Intracellular CTLA4 is also found inregulatory T cells and may play an important role in their functions. T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA4. Genetic variations of CTLA4 have been associated with susceptibility to systemic lupus erythematosus(SLE), Gravesdisease(GRD), Celiac disease type3(CELIAC3) and Hepatitis B virus infection(HBVinfection).
Molecular Mass	14.6 KDa
Apmol Mass	17-30 KDa, reducing conditions
Formulation	Lyophilized from a 0.2 μm filtered solution of 20mM PB, 150mM NaCl, 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	Not tested
Reconstitution	Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage	Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping	The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.
Subcellular Location	Cell membrane; Single-pass type I membrane protein.
Database References	KEGG: mmu:12477 STRING: 10090.ENSMUSP00000027164 UniGene: PMID: 29377881 the investigation of RANK and RANKL as possible novel immunotherapy targets in cancer is a rational approach. Here we have defined the mechanism of action of RANKL-RANK blockade in combination with anti-CTLA4, and provide insight into the combination efficacy observed in the case reports. PMID: 28634284 reveal a novel CTLA-4-mediated pathway to attenuate cytotoxic T-lymphocytes and indicate the importance of post-transcriptional mechanisms in the regulation of anti-tumor immune responses PMID: 28644433 The potential of the CTLA4 and G250 co-expression DNA vaccine. PMID: 28351777 Tregs were observed to regulate CD4(+), but not CD8(+), T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. PMID: 28856392 These results suggest that CD44(+)CD117(+) T cells are stem cells and a specific T-cell phenotype that initially develops in the thymus, but they do not progress through DN3 and DN4 stages, lack a DP stage, and potently suppress T-cell proliferation and modulate the CTLA-4 pathway. PMID: 28279199 data suggest that increased expression of checkpoint blockade molecules PD-1 and CTLA-4 on donor T cells is not sufficient to prevent GvHD, and that cooperation between checkpoint blockade signaling by host cells and donor Tregs is necessary to limit GvHD in allo-HSCT recipients PMID: 28953925 Treg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (TFH)-B cell interactions in germinal centers. Mechanistically, Treg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). PMID: 28892065 CTLA-4 expressed by FOXP3(+) regulatory T cells prevents inflammatory tissue attack and not T-cell priming in arthritis. PMID: 28497863 results are consistent with a complex pathway in which CD28 is the primary driver of Treg proliferation and CTLA-4 functions as the main brake but is also dependent on TCR signals and interactions with CD80/CD86 PMID: 28053234 CTLA-4(+) microvesicles can competitively bind B7 costimulatory molecules on bystander dendritic cells, resulting in downregulation of B7 surface expression. PMID: 26979751 this study shows that miR-155 is modulated by a major dust mite allergen, Dermatophagoides farinae (Df1), and increases CD4+ T cell proliferation through the downregulation of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression PMID: 28110885 CTLA-4 regulates atherosclerosis by suppressing proatherogenic immune responses. PMID: 27055906 Data suggest enhanced clinical benefit from combining CTLA-4 antigen blockade with poxvirus-based active immunotherapy. PMID: 26961085 up-regulated expression correlates with the tolerogenic effect of syngeneic hematopoietic stem cell transplantation PMID: 26311302 Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner PMID: 26950218 CTLA-4 has a regulatory T cell-intrinsic role in limiting peripheral regulatory T cell expansion and activation, and in their capacity to control conventional T cells. PMID: 26371185 The Ctla4 SNP (e2_77A/G) does not alter diabetes susceptibility, but does control mRNA alternative splicing. PMID: 26450994 Sorafenib suppressed the expression of immunosuppressive factors in MDSCs. These data indicate that combination therapy of sorafenib and anti-CTLA-4 Ab may be effective in advanced kidney cancer patients. PMID: 25845968 The co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. PMID: 25238105 The bullseye immunological synapse formation is mediated by CTLA4, and may negatively control T-cell activation as a suppressive synapse. PMID: 25287444 this study reports that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic- T-lymphocyte-associated protein-4 (CTLA-4). PMID: 26084026 Short-term blockade with anti-CTLA-4 antibody in wild-type mice is sufficient to elicit follicular helper T cell generation and germinal center development. The latter occurs in a CD28-dependent manner. PMID: 25548162 CTLA-4 and mTOR down-regulation cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness. PMID: 25624453 role in Treg cell-mediated control of T follicular regulatory cell proliferation, germinal center formation,and of humoral immune responses PMID: 25526312 The study concludes that although the presence of CTLA4 plays a critical role in controlling homeostasis of T cells, its quantitative variation may impose diverse or even opposing effects on distinct lineages of T cells, an optimal sum of which is necessary for preservation of T cell immunity while suppressing tissue damage. PMID: 25246499 cardiomyocytes can express CD80; this expression pattern can resist CTL-mediated lysis through CTLA-4 pathway PMID: 24507064 Alternative splice forms of CTLA-4 induced by antisense mediated splice-switching influences autoimmune diabetes susceptibility in NOD mice. PMID: 24494586 CTLA4(apt) fused to a STAT3-targeting siRNA (CTLA4(apt)-STAT3 siRNA) resulted in internalization into tumor-associated CD8 T cells and silencing of STAT3, which activated tumor antigen-specific T cells in tumor models. PMID: 24892807 results show that CTLA-4 promotes Tc17 differentiation that results in robust Tc17 responses PMID: 24723371 These data suggest that effects associated with and mediated through Tyr201 of CTLA-4s intracellular domain are critical for Treg-cell function. PMID: 24648182 Our in vitro experiments revealed that IL-2 induced expression of CTLA-4 in mouse natural killer cells PMID: 24688023 These novel insights into the differential regulation of CTLA-4 coinhibition on CD4(+) T cells have implications for the immunomodulation of pathologic T cell responses during transplantation and autoimmunity. PMID: 24493820 SOCS3 interacts with CTLA-4 and negatively regulates CTLA-4 levels in T cells, providing a mechanistic explanation for the expansion of regulatory T cells in CD4-SOCS3 during experimental autoimmune uveitis. PMID: 24101549 This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent. PMID: 23872146 Data show coexpression of PD-1 and CTLA-4 correlates with more severe dysfunction of tumor-specific CD8+ T cells. PMID: 23633484 Our results identify CTLA-4 as a key factor that regulates the composition of the Foxp3+ T-cell population in the intestine. PMID: 22910217 The soluble isoform of CTLA-4 is a regulator of T-cell responses. PMID: 23400950 The presence of the alternatively spliced 1/4 CTLA-4 isoform can further promote autoimmunity and autoimmune pathology in lupus-prone mice and suggests that altered splicing of CTLA4 contributes to the expression of autoimmune disease. PMID: 23203389 Li-CTLA-4 expressed at physiologic levels in the CTLA-4-sufficient NOD background suppresses autoimmunity; but, the functionality of the li-CTLA-4 isoform depends on the presence of the full-length molecule to alter effector T cell signaling. PMID: 23293354 CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells and broadens the repertoire of peripheral T cells. PMID: 23267099 pathways by which cAMP regulates CTLA4 expression, focusing on transcriptional activation PMID: 23024062 Findings indicate that CTLA-4-negative regulation of conventional T cells (Tconvs) but not regulatory T cells (Tregs) in immune responses. PMID: 23047820 direct evidence that CTLA4 inhibits spontaneous tumor development PMID: 22777737 CTLA-4 on normal effector CD4-positive T cells completely abrogates the dramatically increased expansion normally experienced by their CTLA-4-deficient counterparts. PMID: 22753941 a potential new role for CTLA-4 in Treg differentiation PMID: 22337882 the importance of intracellular localization for CTLA-4 protein function and reveal that CTLA-4 protein externalization imparts suppressor function to both regulatory and conventional CD4(+) T cells. PMID: 22403258 boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response. PMID: 22412835 The expression of CTLA-4 and PD-1 on T cells correlates with the extent of proinflammatory responses induced during Plasmodium berghei infection, being higher in C57BL/6 than in BALB/c mice. PMID: 22319445 CTLA4-Ig may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy PMID: 22155494

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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.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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