Recombinant Human Interleukin-2 (IL2) (L100F,R101D,L105V,I106V,I112F) (Active)
Product Specs
Note: All of our proteins are standardly shipped with blue ice packs. If you require dry ice shipping, please inform us in advance. Additional fees will apply.
Generally, liquid formulations have a shelf life of 6 months when stored at -20°C/-80°C. Lyophilized forms have a shelf life of 12 months at -20°C/-80°C.
Target Background
- Co-culture with human T lymphocytes induces in vitro maturation of human intestinal organoids. The study identifies STAT3-activating interleukin-2 (IL-2) as the primary factor driving maturation. PMID: 30072687
- This research highlights the levels of IL-2 in bone marrow and blood plasma of aplastic anemia patients and their correlation with disease severity. The findings suggest a potential link between IL-2 and marrow failure in aplastic anemia patients, which could contribute to disease development. Further investigation is needed for a more comprehensive understanding. PMID: 30139310
- This study found no association between IL-2 (T-330G), IL-16 (T-295C), and IL-17 (A-7383G) genotypes and chronic pancreatitis in an Iranian population. PMID: 29400002
- In contrast to certain reports linking polymorphisms in the TGF-beta1 and IL-2 genes to inhibitor development globally, no statistically significant differences were observed in the analysis of alleles and genotypes for TGF-beta and IL-2 genes between inhibitor and non-inhibitor Iranian patients. PMID: 29993342
- The current study emphasizes the potential involvement of the IL-2-330T/G Single Nucleotide Polymorphism in susceptibility to B-Cell Non-Hodgkin Lymphoma. Additionally, IL-10-1082A/G was not identified as a molecular susceptibility marker for B-Cell Non-Hodgkin Lymphoma in Egyptians. PMID: 28713071
- Interleukin-2 (IL-2) is a non-pancreatic autoimmune target in type 1 diabetes. PMID: 27708334
- The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might decrease the risk of oral cancer in the Indian population. PMID: 29664031
- Data reveal that GIF (ORF117 ) acts as a competitive decoy receptor by utilizing binding hotspots that underlie the cognate receptor interactions of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). PMID: 27819269
- CD4(+) T cells exhibited the most significant increase (threefold) in ORMDL3 expression in individuals carrying the asthma-risk alleles. In these cases, ORMDL3 negatively regulated interleukin-2 production. The asthma-risk variants rs4065275 and rs12936231 altered CTCF-binding sites within the 17q21 locus. PMID: 27848966
- The primary mechanism for the elimination of mesenchymal stromal cells is cytotoxicity mediated by NK cells, which depends on IL-2 production. PMID: 29313232
- Uremia patients undergoing maintenance hemodialysis with hospital-acquired infection demonstrated elevated serum inflammatory factors. High-throughput hemodialysis significantly reduced CRP, IL2, and TNFalpha levels in the serum, suggesting its potential benefit in preventing infections in uremia patients. PMID: 29257244
- Simultaneous delivery of multiple proinflammatory payloads to the cancer site conferred protective immunity against subsequent tumor challenges. A fully human homolog of IL2-F8-TNF(mut), retaining selectivity comparable to its murine counterpart when tested on human material, could potentially open new clinical applications for cancer immunotherapy. PMID: 28716814
- The study found that lymphocyte production of IL-2 did not decrease in SLE patients compared to normal subjects. PMID: 29911835
- Peripheral blood Tregs exhibited ineffective utilization of IL-2 and had relatively low STAT5 phosphorylation in active ankylosing spondylitis. PMID: 27901054
- After adjusting for individual cytokine expression levels, qualitative differences in cytokine profiles were observed, characterized by significantly increased TNFalpha and decreased IL-2-expressing T-cell proportions in long-term type-1-diabetes patients. PMID: 28377612
- CD45 acts as a regulator of IL-2 synergy in the NKG2D-mediated activation of immature human NK cells. PMID: 28655861
- Genetic polymorphism is associated with increased susceptibility to chronic spontaneous urticaria in Iran. PMID: 28159384
- PLX4032, a selective BRAF inhibitor, does not have an inhibitory effect on NK cell proliferation in response to cytokines IL-2 or IL-15. PMID: 27563819
- Results indicate that IL-6 and IL-2 were influenced non-specifically by the presence of a mental disorder and by demographic variables such as gender, ethnicity, and BMI. The implications of these findings are discussed, along with the potential long-term impact of the identified interleukin differences on immunologic, inflammatory, neuropsychiatric, and other systems. PMID: 28486207
- Possible associations between the IL-2 polymorphisms +114 T>G (rs2069763) and -330 T>G (rs2069762) and the development of gastric cancer were investigated, and these associations were correlated with the presence of H. pylori. Results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a higher risk of developing gastric cancer, as is the -330G/+114T haplotype. PMID: 28458166
- The overrepresentation of specific alleles, genotypes, and haplotypes in the IL-2 gene in febrile seizure patients could predispose individuals to this condition. PMID: 28843235
- Data suggest that let-7i upregulates IL-2 expression by targeting the promoter TATA-box region, acting as a positive regulator. In HIV-1 infection, let-7i expression in CD4(+) T cells is decreased by attenuating its promoter activity. The reduced let-7i miRNA expression leads to a decline in IL-2 levels, which contributes to CD4(+) T cell death. PMID: 27145859
- IL-2 and IL-6 work synergistically to enhance influenza-specific CD8 T cell generation in response to live influenza virus in aged mice and humans. PMID: 27322555
- This review article aims to determine the roles of IL-2 and IL-2/IL-2R interaction in polyoma BK virus reactivation and PBK-associated nephropathy complications. PMID: 27718431
- Modulating IL-2, IL-4, IFN-gamma, and/or TNF-alpha levels, or employing inhibitors of Erk1/2 or S6K1, may represent a novel approach to preventing BAFF-induced aggressive B-cell malignancies. PMID: 27235588
- Findings indicate that the frequency of Tregs is altered in a large cohort of long-term T1D patients. A significant decrease in CD25 expression and altered IL-2 signaling are characteristic features of Treg populations in long-term diabetic patients and their relatives. PMID: 27560779
- The study suggests a role for circulating IL-2 in liver dysfunction and proposes that a combined assessment of AST/ALT in conjunction with IL-2 in the early stages of symptomatic DENV infection could be useful for predicting severe forms of dengue. PMID: 27155816
- Lymphocytes incubated in the presence of IL-2 lose their capacity for chemotaxis but acquire antitumor activity. PMID: 28429264
- The central biological role of the novel IL-2-R/Lck/PLCgamma/PKCtheta;/alphaPIX/Rac1/PYGM signaling pathway is directly related to the regulation of fundamental cellular processes such as T cell migration and proliferation. PMID: 27519475
- F42K can circumvent the expansion and negative immunoregulatory effects of highly suppressive ICOS+ Tregs, while promoting NK cell expansion and function. F42K also induces a unique gene expression profile and does not activate many IL2-induced genes, although it has the capacity to activate NK cells and NK cell-associated activation genes, costimulatory molecules, and NK-mediated cytolytic function. PMID: 27697858
- A chimeric fusion protein of interleukin 2 (IL2) and its receptor interleukin 2 receptor, beta protein (IL2Rbeta), enhances the antitumor activity of natural killer NK92 cells. PMID: 28916655
- Il2 was not a useful discriminative marker for active tuberculosis among pulmonary tuberculosis suspects. PMID: 27450011
- IL-2 and IL-10 can work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8(+) T cells, an effect that is suppressible by CD4(+)CD25(+) Treg cells. PMID: 28274688
- Results indicate that IL-23 is responsible for the main aspects of human and murine lupus, including the expansion of double negative T cells, decreased IL-2, and increased IL-17 production. PMID: 28646040
- The study reports efficient retroviral vector transduction of primary human natural killer cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21 for cancer immunotherapy. PMID: 28802832
- Upon ligation of the T-cell antigen receptor (TCR), the TCR associates with and transactivates CXCR4 through phosphorylation of S339-CXCR4 to activate a PREX1-Rac1-signaling pathway that stabilizes interleukin-2 (IL-2), IL-4, and IL-10 messenger RNA (mRNA) transcripts. PMID: 28694325
- IL2 induces disruption of adherens junctions, accompanied by cytoskeletal reorganization, ultimately leading to increased endothelial cell permeability. PMID: 27601468
- Findings enhance our understanding of the distinct modes of action between IL-2 and IL-15, highlighting how, despite sharing the CD122/CD132 receptor, they elicit such diverse immune responses. PMID: 28507024
- DNA-PKcs is a potent regulator of IL-2 production in T lymphocytes. PMID: 28750002
- Yeast-expressed human IL-2 fusion toxin effectively targeted CD25(+) cutaneous T cell lymphoma. PMID: 28551309
- The study provides evidence that membrane-coated microvesicles released by apoptotic neutrophils suppress a subset of resting Th cells by downregulating IL-2 and IL-2R expression. PMID: 28295230
- In T1D, low IL-2 responsiveness was most pronounced in memory T effector cells. Reduced IL-2 responses in memory T effector cells were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. PMID: 28645874
- The elevated level of IL-2+ and IL-21+ T cells and a positive correlation between IL-21+ cells with clinical activity index in ulcerative colitis patients may contribute to the pathogenesis of the disease. PMID: 28685527
- The analysis focuses on the contribution of IL2Rgamma to the dynamic formation of IL2-IL2R complexes. PMID: 27195783
- The absence of local IL-2 enhances regulatory T-cell susceptibility to Fas-mediated apoptosis induced by epithelial cells. PMID: 26928938
- The IL-2 rs2069762 G allele appeared to be a protective mutation against aplastic anemia, but no significant differences were found in the other four IL-2 and Il-8 SNPs studied. PMID: 28268223
- Pristimerin inhibits IL-2-induced T cell activation and the generation of lymphokine-activated killer cells by disrupting multiple cell signaling pathways triggered by IL-2. PMID: 28471123
- Combination therapy using IL-2 or induced killer cells was found to be effective in treating NSCLC and improving overall survival. Further analysis of trials with adequate information and data is needed to confirm these findings. PMID: 27748271
- Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. PMID: 27356894
- Ochratoxin A mediates MAPK activation, modulates IL-2 and TNF-alpha mRNA expression, and induces apoptosis through mitochondria-dependent and mitochondria-independent pathways in the human CD4 positive T-cell lymphoma cell line. PMID: 27193732
Q&A
Biological Foundation of IL-2
Interleukin-2 is a 15.5-16 kDa protein cytokine that functions as a critical immune signaling molecule . It regulates the activities of leukocytes, particularly lymphocytes, responsible for immune responses . The primary function of IL-2 is to stimulate the growth and activity of helper, cytotoxic, and regulatory T cells . In its natural context, IL-2 mediates responses to microbial infections and helps discriminate between "self" and "non-self" entities .
IL-2 exerts its biological effects by binding to IL-2 receptors expressed on lymphocytes . These receptors exist in three forms with varying affinities:
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Low-affinity receptor: α subunit (CD25) alone (~10⁻⁸ M)
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Intermediate-affinity receptor: β and γ subunits (CD122/CD132) (~10⁻⁹ M)
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High-affinity receptor: trimeric complex of α, β, and γ subunits (CD25/CD122/CD132) (~10⁻¹¹ M)
The differential expression of these receptor components on various immune cell populations determines their responsiveness to IL-2. Memory CD8+ T cells and natural killer (NK) cells primarily express the intermediate-affinity dimeric receptor, while regulatory T cells and activated T cells express high levels of the trimeric high-affinity receptor .
Rationale for IL-2 Mutation Engineering
Despite IL-2's promising immunotherapeutic potential, particularly for cancer treatment, its clinical application has been limited by severe toxicity following binding to its high-affinity IL-2Rα (CD25) . This toxicity manifests as vascular leak syndrome, pulmonary edema, and other serious adverse effects that restrict dosing and efficacy .
The engineered variant with L100F, R101D, L105V, I106V, and I112F mutations was specifically designed to address these limitations by modifying IL-2's receptor binding profile . Molecular dynamic simulations revealed that these mutations significantly reduce the protein's affinity for IL-2Rα while maintaining functional interaction with the intermediate-affinity receptor components .
Mechanistic Basis of Modified Activity
The strategic mutations alter the interaction surface between IL-2 and CD25 without compromising the core biological activity of the cytokine . Flow cytometry analysis using anti-CD25 monoclonal antibodies confirmed the reduced affinity of this mutant for IL-2Rα compared to wild-type IL-2 . This selective binding modification shifts the activation profile toward cytotoxic CD8+ T cells and NK cells rather than regulatory T cells and endothelial cells, which predominantly express high levels of CD25 .
Immune Cell Activation Profile
Experimental studies demonstrate that the mutant IL-2 (K35A, E61A, and F42A - a similar design approach) exhibits altered stimulation patterns compared to wild-type IL-2 . The engineered variant shows:
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Reduced proliferation rate of peripheral blood mononuclear cells (PBMCs) compared to wild-type IL-2, consistent with its lower interaction with the high-affinity receptor
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Decreased interferon-gamma (IFN-γ) secretion levels from stimulated immune cells, aligning with findings from similar IL-2 mutants (R38A and F42K) that primarily target the intermediate-affinity receptor
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Enhanced activation of CD8+ T cells with increased expression of effector molecules like Granzyme B, critical for anti-tumor activity
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Altered distribution of activated T cells in lymphoid tissues, potentially improving targeted immune responses
Anti-tumor Activity
The modified binding characteristics translate to improved therapeutic potential for cancer treatment. Studies with similar IL-2 mutants demonstrated:
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Superior expansion of cytotoxic T cells relative to regulatory T cells, creating a more favorable immune environment for tumor elimination
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Enhanced anti-tumor responses in vivo with reduced systemic toxicity compared to wild-type IL-2 treatment
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Improved therapeutic index by maintaining efficacy while reducing the side effects that typically limit standard IL-2 therapy
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Potential for combination with other immunotherapeutic approaches due to reduced toxicity profile
Structural and Pharmaceutical Properties
The recombinant human IL-2 variant with L100F, R101D, L105V, I106V, and I112F mutations is typically produced as a purified protein with the following characteristics:
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Formulation as a lyophilized product from a 0.2 μm filtered 4mM HCl solution
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Storage requirements at -20°C or -80°C to maintain stability
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Endotoxin levels below 1.0 EU/μg, ensuring safety for experimental and potential clinical applications
The protein sequence maintains the core structure of human IL-2 while incorporating the five specific amino acid substitutions that confer its modified binding properties .
Comparative Advantage Over Wild-type IL-2
The strategic mutations in this IL-2 variant offer several potential advantages over the wild-type molecule for therapeutic applications:
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Reduced systemic toxicity due to decreased activation of high-affinity IL-2R-expressing cells implicated in adverse effects
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Preferential stimulation of cytotoxic immune cells (CD8+ T cells and NK cells) that mediate anti-tumor responses
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Diminished expansion of regulatory T cells that can suppress anti-tumor immunity
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Improved tissue distribution with reduced pulmonary and vascular complications
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Potential for higher dosing regimens due to enhanced safety profile
These properties address the key limitations that have restricted the clinical utility of wild-type IL-2 in cancer immunotherapy, potentially offering a more effective treatment option with a wider therapeutic window.
