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B7-H2/ICOS L 和 ICOS 可促进 T 细胞活化

B7-H2 与 ICOS 结合可产生 T 细胞共刺激信号

ICOS 是另一种主要在活化 T 细胞上表达的 CD28 家族受体。它与抗原呈递细胞上表达的 B7-H2/ICOS L 结合,促进 T 细胞增殖,并促进 Th1 和 Th2 细胞生成细胞因子。1与此相对的是,ICOS/ICOS L 通路也已被证明可增强调节性 T 细胞的发育和活性,这表明其也可能具有促肿瘤作用。2, 3在黑色素瘤的小鼠模型中,ICOS 或 ICOS L 敲除小鼠对抗 CTLA-4 治疗的应答降低,而在其他肿瘤模型中,ICOS 共刺激联合 CTLA-4 阻断被证明可增强抗肿瘤免疫应答。4-7与这些结果相反,据报告,ICOS 和 ICOS L 也会在不同类型的癌细胞和肿瘤浸润免疫细胞上表达,与肿瘤进展和总生存期较差有关。2, 8, 9因此,有关靶向 ICOS/ICOSL 通路的激动剂和拮抗剂抗体对于癌症治疗的疗效,人们仍在进行评估。5

B7-H2 通过与 ICOS 结合来调节 T 细胞活化

Binding of B7-H2/ICOS L to T cell-expressed ICOS delivers a T cell co-stimulatory signal that enhances Th1 and Th2 cytokine production.

B7-H2/ICOS L 与 T 细胞表达的 ICOS 结合可产生 T 细胞共刺激信号,从而增强 Th1 和 Th2 细胞因子的生成。TCR 活化后,ICOS 在活化 T 细胞上表达,并在 CD28 共刺激下进一步增强。ICOS 与其在抗原呈递细胞 (APC) 上表达的配体 B7-H2/ICOS L 结合,可产生共刺激信号,促进 Th1 和 Th2 细胞生成细胞因子。与此相对的是,在肿瘤微环境中,ICOS L/ICOS 信号转导也可能增强调节性 T 细胞的发育和活性,从而可能抑制抗肿瘤的免疫应答。

R&D Systems B7-H2 和 ICOS 蛋白生物活性和纯度评估

Bioactivity assay data showing R&D Systems Recombinant Human B7-H2/ICOS L Fc Chimera stimulates anti-CD3-induced human T cell proliferation.

B7-H2/ICOS L 可刺激抗 CD3 诱导的人 T 细胞增殖。用固定化小鼠抗人 CD3 ε 单克隆抗体(R&D Systems,目录号 MAB100;20 ng/mL)和指定浓度的重组人 B7-H2/ICOS L Fc 嵌合体(R&D Systems,目录号 165-B7)培育人 T 细胞,然后对细胞增殖情况进行评估。这一作用的 ED50 通常为 0.3-1.2 ug/mL。

Purity of Recombinant Human ICOS assessed by CE-SDS on Maurice under reducing (R) and non-reducing (NR) conditions and visualized in Compass for iCE software.

在 MauriceTM 系统上通过 CE-SDS 评估重组人 ICOS 的纯度。Maurice 系统上,通过毛细管电泳 (CE)-SDS,在还原 (R) 和非还原 (NR) 条件下评估重组人 ICOS His 标签(R&D Systems,目录号 9865-CS)的纯度,在 Compass for iCE 软件中进行可视化。凝胶视图以套印小图的形式显示,相对迁移时间 (RMT) 显示在电泳图谱上凝胶条带的最右侧。

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