日本血吸虫分泌型抗原T细胞表位的预测研究

发布时间：2018-10-13 10:38

【摘要】：获得高效安全的疫苗一直是血吸虫病控制研发领域中亟待解决的热点和难点问题之一。大量免疫机制研究表明：在辐照致弱尾蚴免疫小鼠等动物模型中，其诱导的高保护力主要是由CD4+T细胞介导的细胞免疫。筛选到上述模型中发挥保护性细胞免疫效应作用的分子或者T细胞表位，应当是血吸虫疫苗研究的可能的突破点之一。而基于可靠的免疫信息学实验与理论的反向疫苗学技术与常规方法相比，可以节省大量的实验时间和经费，可能成为快速发现血吸虫保护性T细胞抗原或表位的有力工具。应用反向疫苗学策略快速有效地发现保护性抗原和表位要解决的关键问题主要有：怎样从大量序列中筛查出可能的候选分子；怎样准确地进行MHC结合肽的预测。本研究以116个日本血吸虫全长cDNA序列和71个EST序列为样本，围绕解决上述二个关键技术问题开展工作，研究内容包括候选序列的注释与分析以及T细胞表位的预测和初步鉴定。准确地识别出DNA序列的蛋白质编码区是开展T细胞表位筛选工作的前提。鉴于目前还没有供一般实验室使用的标准程序来进行日本血吸虫DNA序列的蛋白质编码区的识别，使得各实验室所提交的序列的编码区识别出现一些差异，本研究将基于序列内部特征的序列谱分析和马尔科夫模型等方法与基于序列外部特征的方法如编码区起始位点和终止位点的识别等相结合，即采用多服务器综合分析流程，，对上述样本序列进行了分析。对116条全长cDNA序列的预测结果表明，仅有5％的序列(6条)与中国国家人类基因组南方研究中心(以下称南方中心)的预测结果完全不同；有8.6％(及1.7％)的序列的预测读码框与南方中心预测的相同，但长度短于(及长于)南方中心注释结果；其余预测结果与南方中心注释的完全相同。对71条EST序列组装后得到非冗余的51条EST序列，成功地用上述流程对其进行了蛋白质编码区的识别。提示本研
[Abstract]:Obtaining efficient and safe vaccine is one of the hot and difficult problems in schistosomiasis control research and development. A large number of studies on immunological mechanism showed that the high protective effect of cercariae induced by irradiation on mice was mainly mediated by CD4 T cells. The screening of molecules or T cell epitopes that play a protective role in the above models should be one of the possible breakthrough points in Schistosoma japonicum vaccine research. The reverse vaccine technique based on reliable immuno-informatics experiment and theory can save a lot of experimental time and money compared with the conventional method. It may be a powerful tool for rapid detection of protective T cell antigen or epitope of Schistosoma japonicum. The key problems to be solved by using reverse vaccine strategy to find protective antigens and epitopes quickly and effectively are: how to screen out possible candidate molecules from a large number of sequences and how to accurately predict MHC binding peptides. In this study, 116 full-length cDNA sequences and 71 EST sequences of Schistosoma japonicum were used as samples to solve the above two key technical problems, including the annotation and analysis of candidate sequences and the prediction and preliminary identification of T cell epitopes. Accurate identification of protein coding regions of DNA sequences is a prerequisite for T cell epitope screening. In view of the fact that there are currently no standard procedures for the identification of protein coding regions of Schistosoma japonicum DNA sequences for general laboratories, there are some differences in the identification of coding regions of the sequences submitted by laboratories, In this study, we combine the sequence spectrum analysis and Markov model based on the internal features of the sequence with the methods based on the external features of the sequence, such as the identification of the starting and terminating sites of the coding region, that is, the multi-server comprehensive analysis process. The above sample sequences are analyzed. The prediction results of 116 full-length cDNA sequences showed that only 5% of the sequences (6 sequences) were completely different from those of the National Center for Human Genome Southern Research (hereinafter referred to as the Southern Center). The predicted code frames of 8.6% (and 1.7%) of the sequences are the same as those predicted by the South Center, but the length is shorter than (and longer than) the results of the South Center annotation, and the other prediction results are exactly the same as those of the Southern Center annotation. After 71 EST sequences were assembled, 51 non-redundant EST sequences were obtained, and the protein coding regions were successfully identified by the above procedures. Prompt this research
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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