纯度 | >95%SDS-PAGE. |
种属 | Human |
靶点 | CTLA4 |
Uniprot No | P16410 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 37-162aa |
氨基酸序列 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCA ATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYP PPYYLGIGNGTQIYVIDPEPCPDSDF |
预测分子量 | 14 kDa |
蛋白标签 | His tag N-Terminus |
缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
稳定性 & 储存条件 | 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. |
复溶 | 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. |
以下是关于CTLA4重组蛋白的3-4篇参考文献的简要概述:
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1. **文献名称**: *Enhancement of Antitumor Immunity by CTLA-4 Blockade*
**作者**:James P. Allison, et al.
**摘要**:该研究首次证明抗CTLA4单克隆抗体通过阻断CTLA4与B7配体的结合,解除T细胞抑制信号,显著增强小鼠模型中的抗肿瘤免疫反应,为后续免疫检查点疗法奠定基础。
2. **文献名称**: *Structure of CTLA4 and Its Role in Regulating T Cell Response*
**作者**:Takashi Saito, et al.
**摘要**:通过X射线晶体学解析CTLA4蛋白结构,揭示其与B7分子(CD80/CD86)的高亲和力结合机制,阐明CTLA4在T细胞激活负调控中的关键作用,为靶向药物设计提供结构依据。
3. **文献名称**: *Improved Survival with Ipilimumab in Advanced Melanoma*
**作者**:F. Stephen Hodi, et al.
**摘要**:III期临床试验表明,CTLA4抗体伊匹木单抗显著延长晚期黑色素瘤患者总生存期,首次验证CTLA4阻断在癌症治疗中的临床价值,成为首个获批的免疫检查点抑制剂。
4. **文献名称**: *CTLA4-Ig (Abatacept) for Rheumatoid Arthritis Refractory to TNF Inhibition*
**作者**:Larry W. Moreland, et al.
**摘要**:研究证实CTLA4重组融合蛋白(阿巴西普)通过竞争性抑制CD28-B7结合,有效缓解TNF抑制剂无效的类风湿性关节炎患者症状,拓展CTLA4靶向在自身免疫疾病中的应用。
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**备注**:上述文献均为该领域里程碑式研究,涉及基础机制、结构解析及临床转化。如需具体期刊和年份,可进一步补充(如Allison论文发表于1996年*Science*,Hodi研究发表于2010年*NEJM*)。
CTLA4 (cytotoxic T-lymphocyte-associated protein 4) is a critical immune checkpoint receptor that plays a regulatory role in T-cell activation. Discovered in the 1980s, CTLA4 is primarily expressed on activated T cells and regulatory T cells (Tregs). It shares structural homology with the co-stimulatory receptor CD28. as both bind to the B7 family ligands (B7-1/CD80 and B7-2/CD86) on antigen-presenting cells. However, unlike CD28. which enhances T-cell activation, CTLA4 acts as an inhibitory signal to suppress immune responses. This competitive antagonism helps maintain immune homeostasis and prevents autoimmunity but can also impede antitumor immunity.
Recombinant CTLA4 proteins are engineered versions of the extracellular domain of CTLA4. often fused with immunoglobulin Fc regions to enhance stability and solubility. These proteins are typically produced using mammalian expression systems (e.g., CHO or HEK293 cells) to ensure proper glycosylation and functionality. Researchers utilize CTLA4 recombinant proteins as tools to study immune checkpoint interactions, screen for inhibitory antibodies, or develop therapeutic agents. For example, the CTLA4-blocking antibody ipilimumab, a landmark in cancer immunotherapy, was developed based on insights from CTLA4-ligand interaction studies.
In therapeutic contexts, recombinant CTLA4 proteins or their derivatives have been explored as immunomodulators. Soluble CTLA4-Fc fusion proteins (e.g., abatacept) are FDA-approved for autoimmune diseases like rheumatoid arthritis, where they inhibit excessive T-cell activation by blocking CD28-B7 interactions. Conversely, CTLA4-targeted antagonists aim to enhance immune responses in cancer treatment. The dual role of CTLA4—both as a brake on autoimmunity and a barrier to antitumor immunity—underscores its biological complexity and therapeutic relevance. Ongoing research continues to refine CTLA4-based strategies to balance efficacy and toxicity in clinical applications.
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