EGFP标记的小鼠K～b分子在RAW246.7中的表达及其交叉递呈功能的初步研究

发布时间：2018-05-07 02:19

本文选题：交叉递呈 + 绿色荧光蛋白　；参考：《第三军医大学》2005年硕士论文

【摘要】： T淋巴细胞识别由主要组织相容性复合物(MHC)I或II类分子递呈的抗原肽片段。对于MHC-I类分子而言,经典的抗原递呈理论认为胞浆内合成的蛋白质抗原在胞浆中蛋白酶体的作用下被裂解为小的肽段,随后在抗原加工相关转运体(TAP)的作用进入内质网(ER),与其中的MHC-I类分子相结合,并形成稳定的MHC-I-肽复合物,然后从ER转运到高尔基体和细胞膜表面,供CD8+T细胞识别。而外源性抗原经胞吞或胞饮作用进入抗原递呈细胞(APC)的内体系统,被其中的酸敏蛋白酶降解,然后与位于晚期内体和溶酶体样结构中的MHC-II类分子相结合,并由其递呈给CD4+T细胞。然而,26年前在器官移植中发现,宿主的抗原递呈细胞可以激发宿主对供者细胞次要组织相容性抗原的免疫应答,这一现象现被称为交叉递呈。大量研究表明,多种抗原均可经此途径引起CD8+T细胞的免疫应答。交叉递呈在清除不能感染APC的病毒、自身MHC-I类分子下调的肿瘤组织以及维持外周耐受方面都发挥着重要作用,因此,阐明交叉递呈的细胞和分子机制是十分必要的。可为临床疾病的治疗及疫苗设计提供新思路。对于交叉递呈的胞内途径一直以来有两种认识。其中之一认为外源性抗原进入内吞囊泡后依靠特殊的转运机制或者内吞囊泡膜的破裂而释放其中的抗原到胞浆中,然后沿着经典的MHC-I类途径被递呈给CD8+T细胞。另一种观点认为交叉递呈发生于内体系统中,抗原被其中酸敏的蛋白酶体水解,和由细胞膜上循环而至的MHC-I类分子相结合,随后被转运到细胞表面。最近,有文献报道在外源性抗原的交叉递呈过程中,ER可以和吞噬体相互融合,后者从ER中获得MHC-I类递呈途径所需要的各种分子。这一模型的提出为交叉递呈的研究提供了新思路。关于交叉递呈中MHC-I类分子及其和抗原肽形成复合物后的转运途径还不明确,上述模型也多是从生化角度加以论证。有研究表明部分病毒以及肿瘤组织之所以不能被机体免疫系统有效识别,就是因为其干扰了胞内MHC-I类分子至胞膜的转运,而并非以前认为的抑制MHC-I类分子的合成。因此,明确MHC-I类分子在交叉递呈过程
[Abstract]:T lymphocytes recognize antigenic peptide fragments presented by major histocompatibility complexes (MHCI or II). For MHC-I molecules, the classical antigen-presenting theory suggests that the protein antigens synthesized in the cytoplasm are split into small peptides under the action of the proteasome in the cytoplasm. Then TAP, a transporter associated with antigen processing, enters the endoplasmic reticulum (ER), binds to the MHC-I molecules, and forms a stable MHC-I- peptide complex, which is then transported from ER to Golgi apparatus and cell membrane for recognition by CD8 T cells. The exogenous antigens enter the inner system of antigen-presenting cells through cytosolic or cytosolic action, and are degraded by acid-sensitive proteases, and then combined with MHC-II molecules located in the late inosomes and lysosomal structures. And it was presented to CD4 T cells. However, in organ transplantation 26 years ago, it was found that host antigen-presenting cells can stimulate the host's immune response to donor cell secondary histocompatibility antigen, which is now known as cross-presentation. A large number of studies have shown that many kinds of antigens can induce immune response of CD8 T cells in this way. Cross-presentation plays an important role in the clearance of viruses that cannot be infected with APC, the down-regulation of tumor tissues by their own MHC-I molecules and the maintenance of peripheral tolerance. Therefore, it is necessary to elucidate the cellular and molecular mechanisms of cross-presentation. It can provide a new idea for the treatment of clinical diseases and vaccine design. There have been two understandings of the intracellular pathway of cross-presentation. One of them suggested that exogenous antigens were released into the cytoplasm by special transport mechanism or rupture of endocytic vesicle membrane, and then presented to CD8 T cells along the classical MHC-I pathway. In another view, cross-presentation occurs in the inner body system, in which the antigen is hydrolyzed by the acid-sensitive proteasome, combined with the MHC-I molecules circulating on the cell membrane, and then transported to the cell surface. Recently, it has been reported that ER can fuse with phagocysts during cross-presentation of exogenous antigens, and the latter can obtain various molecules needed for the MHC-I presenting pathway from ER. This model provides a new idea for the research of cross-presentation. The transport pathways of MHC-I molecules and their complexes with antigenic peptides in cross-presentation are not clear, and the above models are also demonstrated from the biochemical point of view. Some studies have shown that some viruses and tumor tissues can not be effectively recognized by the body's immune system because it interferes with the transport of MHC-I class molecules to the cellular membrane, rather than inhibiting the synthesis of MHC-I class molecules as previously thought. Therefore, it is clear that MHC-I molecules in the cross-presentation process
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

【相似文献】