鼠抗人2IgB7-H3功能性单克隆抗体的研制及其生物学功能的初步研究

发布时间：2018-02-14 02:14

本文关键词： B7-H3 杂交瘤单克隆抗体表达谱 DCs 肿瘤细胞　出处：《苏州大学》2006年硕士论文　论文类型：学位论文

【摘要】：B7-H3分子是最新发现的B7家族的新成员,属于B7超家族成员,为I型跨膜球蛋白,分子量为45-110kDa,编码361-534个氨基酸。该分子具有IgV和IgC样区、跨膜区、胞浆区及信号肽区。B7-H3 mRNA有较广泛的组织表达谱,在某些恶性肿瘤细胞上也有较高的表达,其相应的受体尚未发现,有文献报道,B7-H3对T细胞存在两种不同的效应∶刺激或者抑制效应。B7-H3能够刺激T细胞的增殖,使CTL的活性增加,特异性提高IFN-γ分泌表达;但也有研究者发现,B7-H3能抑制CD4+ T细胞的增殖及IFN-γ分泌表达。更为重要的是B7-H3有2IgB7-H3和4IgB7-H3两个异构体,其表达的差异及生物学意义尚需深入研究。目前本校医学生物技术研究所已研制了既能识别4IgB7-H3又能识别2IgB7-H3的两株单抗,鉴于此,研究共刺激分子2IgB7-H3的特异性单抗更加有助于该共刺激信号学功能的研究,并且在肿瘤免疫及自身免疫性疾病的治疗中均具有潜在的应用价值。本研究成功研制了一株新的鼠抗人2IgB7-H3功能性单克隆抗体7D7,并对其生物学特性及生物学功能做了初步的鉴定。通过对比2IgB7-H3单克隆抗体和4IgB7-H3单克隆抗体的生物学特性及其功能,将为理解B7-H3分子在信号调节途径、免疫应答提供新的研究视角,具有一定的应用前景。研究目的:制备鼠抗人2IgB7-H3分子的单克隆抗体(mAb)并对其进行相关生物学特性的鉴定;利用自主研制的抗人2IgB7-H3 mAb,研究B7-H3在DCs上的表达及其信号途径在DCs上的生物学作用,同时鉴定2IgB7-H3和4IgB7-H3单克隆抗体的肿瘤细胞表达谱的生物学差异和单抗7D7在肿瘤免疫中的生物学作用。
[Abstract]:B7-H3 molecule is a new member of the newly discovered B7 family. It belongs to the B7 superfamily. It is a type I transmembrane globulin with a molecular weight of 45-110 kDaand encodes 361-534 amino acids. The molecule has IgV and IgC like regions and transmembrane regions. The cytoplasmic domain and signal peptide region. B7-H3 mRNA have extensive tissue expression profile and high expression in some malignant tumor cells. The corresponding receptors have not been found yet. It has been reported that there are two different effects of B7-H3 on T cells: stimulating or inhibiting effect. B7-H3 can stimulate the proliferation of T cells, increase the activity of CTL, and increase the expression of IFN- 纬 specifically. However, some researchers have found that B7-H3 can inhibit the proliferation of CD4 T cells and the expression of IFN- 纬. More importantly, B7-H3 has 2IgB7-H3 and 4IgB7-H3 isomers. The difference of its expression and its biological significance need to be further studied. At present, two McAbs have been developed by the Institute of Medical Biotechnology, which can recognize both 4IgB7-H3 and 2IgB7-H3. The study of the specific monoclonal antibody of the costimulatory molecule 2IgB7-H3 is more helpful to the study of the signal function of the costimulatory molecule 2IgB7-H3. In this study, a new mouse functional monoclonal antibody against human 2IgB7-H3, 7D7, was successfully developed, and its biological characteristics and biological functions were studied. The biological characteristics and functions of monoclonal antibody 2IgB7-H3 and monoclonal antibody 4IgB7-H3 were compared. It will provide a new perspective for the understanding of B7-H3 molecule in signal regulation pathway and immune response, and will have a certain application prospect. Objective: to prepare mouse anti-human 2IgB7-H3 monoclonal antibody (mAb) and to identify its biological characteristics, and to study the expression of B7-H3 on DCs and the biological effect of its signal pathway on DCs by using the self-developed anti-human 2IgB7-H3 mAb. The biological differences of tumor cell expression profiles of monoclonal antibodies 2IgB7-H3 and 4IgB7-H3 and the biological role of monoclonal antibody 7D7 in tumor immunity were also identified.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392;Q813.2

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