CONSTRUCTION, PURIFICATION, AND FUNCTIONAL INCORPORATION ON TUMOR-CELLS OF GLYCOLIPID-ANCHORED HUMAN B7-1 (CD80)
CONSTRUCTION, PURIFICATION, AND FUNCTIONAL INCORPORATION ON TUMOR-CELLS OF GLYCOLIPID-ANCHORED HUMAN B7-1 (CD80)
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DOI：
10.1073/pnas.92.17.8059
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
SELVARAJ, P
中科院分区：
文献类型：
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作者：
MCHUGH, RS;AHMED, SN;SELVARAJ, P
要产生有效的细胞介导的免疫反应，T细胞至少需要两个信号。其一是T细胞受体与含肽的主要组织相容性复合体分子的结合。另一种信号可以由抗原提呈细胞上的各种分子传递，如B7-1(CD80)。许多肿瘤细胞通过不表达这些共刺激分子来逃避免疫识别，将B7基因导入一些小鼠肿瘤细胞可以实现免疫识别和随后的亲本肿瘤排斥反应。我们已经研究了一种将B7-1引入肿瘤细胞表面的替代方法。这种方法包括纯化的糖基磷脂酰肌醇(GPI)锚定蛋白，它可以自发地将其脂尾结合到细胞膜中。我们已经创造并纯化了一种GPI锚定的B7-1分子(称为GPI-B7)，它能够与其同源配体CD28结合，并在短暂的孵育后将自己整合到肿瘤细胞膜上。用GPI-B7重组的肿瘤细胞可以提供刺激T细胞所需的共刺激信号。这些发现表明了一种将新蛋白引入细胞膜以创建一种有效的肿瘤疫苗的方法，该疫苗可能用于人类免疫治疗。
To generate a potent cell-mediated immune response, at least two signals are required by T cells. One is engagement of the T cell receptor with peptide-bearing major histocompatibility complex molecules. The other signal can be delivered by various molecules on the antigen-presenting cell, such as B7-1 (CD80). Many tumor cells escape immune recognition by failing to express these costimulatory molecules, Transfection of the B7 gene into some murine tumor cells allows for immune recognition and subsequent rejection of the parental tumor. We have studied an alternative approach for the introduction of B7-1 onto the surface of tumor cells. This method involves purified glycosyl-phosphatidylinositol (GPI)-anchored proteins which can spontaneously incorporate their lipid tail into cell membranes. We have created and purified a GPI-anchored B7-1 molecule (called GPI-B7) which is able to bind its cognate ligand, CD28, and incorporate itself into tumor cell membranes after a short incubation. Tumor cells that have been reconstituted with GPI-B7 can provide the costimulatory signal needed to stimulate T cells. These findings suggest an approach for the introduction of new proteins onto cell membranes to create an effective tumor vaccine for potential use in human immunotherapy.