Glycosylphosphatidylinositol-modified murine B7-1 and B7-2 retain costimulator function.
Glycosylphosphatidylinositol-modified murine B7-1 and B7-2 retain costimulator function.
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DOI：
10.4049/jimmunol.155.12.5498
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发表时间：
1995-12
影响因子：
4.4
通讯作者：
E. Brunschwig;E. Levine;U. Trefzer;M. Tykocinski
中科院分区：
文献类型：
--
作者：
E. Brunschwig;E. Levine;U. Trefzer;M. Tykocinski
小鼠B7-1和B7-2细胞表面共刺激因子的糖基磷脂酰肌醇（GPI）修饰变体通过与来自衰变加速因子（decay-accelerating factor，DIF）的替代GPI修饰信号序列嵌合产生。GPI锚定通过证明嵌合多肽在免疫荧光/流式细胞术和免疫沉淀分析中的磷脂酰肌醇特异性磷脂酶C（PI-PLC）敏感性来验证。各种GPI修饰的嵌合B7-1：β和B7-2：β多肽在体外增殖测定和体内触发细胞毒性测定中均显示出保留共刺激分子功能。研究结果表明，B7-1和B7-2的共刺激分子功能不依赖于天然疏水跨膜锚定。此外，GPI修饰的变体在增强鼠T淋巴瘤系EL-4的免疫原性中的功能性提示了用于产生APC为中心的免疫治疗剂（包括细胞癌症疫苗）的新途径，其基于GPI修饰的共刺激因子的蛋白质转移。
Glycosylphosphatidylinositol (GPI)-modified variants of murine B7-1 and B7-2 cell surface costimulators were produced via chimerization with alternative GPI-modification signal sequences from decay-accelerating factor (DAF). GPI anchorage was verified by demonstrating phosphatidylinositol-specific phospholipase C (PI-PLC) sensitivity of the chimeric polypeptides in both immunofluorescence/flow-cytometric and immunoprecipitation analyses. The various GPI-modified chimeric B7-1:DAF and B7-2:DAF polypeptides were shown to retain costimulator function, in both an in vitro proliferation assay and an in vivo triggering of cytotoxicity assay. The findings indicate that costimulator function for both B7-1 and B7-2 is not dependent upon native hydrophobic transmembrane anchorage. Moreover, the functionality of the GPI-modified variants in enhancing the immunogenicity of the murine T lymphoma line EL-4 suggests a novel route for generating APC-centered immunotherapeutics, including cellular cancer vaccines, that is based upon protein transfer of GPI-modified costimulators.