【摘要】：獲得高效安全的疫苗一直是血吸蟲病控制研發(fā)領(lǐng)域中亟待解決的熱點(diǎn)和難點(diǎn)問題之一。大量免疫機(jī)制研究表明：在輻照致弱尾蚴免疫小鼠等動(dòng)物模型中，其誘導(dǎo)的高保護(hù)力主要是由CD4+T細(xì)胞介導(dǎo)的細(xì)胞免疫。篩選到上述模型中發(fā)揮保護(hù)性細(xì)胞免疫效應(yīng)作用的分子或者T細(xì)胞表位，應(yīng)當(dāng)是血吸蟲疫苗研究的可能的突破點(diǎn)之一。而基于可靠的免疫信息學(xué)實(shí)驗(yàn)與理論的反向疫苗學(xué)技術(shù)與常規(guī)方法相比，可以節(jié)省大量的實(shí)驗(yàn)時(shí)間和經(jīng)費(fèi)，可能成為快速發(fā)現(xiàn)血吸蟲保護(hù)性T細(xì)胞抗原或表位的有力工具。 應(yīng)用反向疫苗學(xué)策略快速有效地發(fā)現(xiàn)保護(hù)性抗原和表位要解決的關(guān)鍵問題主要有：怎樣從大量序列中篩查出可能的候選分子；怎樣準(zhǔn)確地進(jìn)行MHC結(jié)合肽的預(yù)測(cè)。本研究以116個(gè)日本血吸蟲全長(zhǎng)cDNA序列和71個(gè)EST序列為樣本，圍繞解決上述二個(gè)關(guān)鍵技術(shù)問題開展工作，研究?jī)?nèi)容包括候選序列的注釋與分析以及T細(xì)胞表位的預(yù)測(cè)和初步鑒定。 準(zhǔn)確地識(shí)別出DNA序列的蛋白質(zhì)編碼區(qū)是開展T細(xì)胞表位篩選工作的前提。鑒于目前還沒有供一般實(shí)驗(yàn)室使用的標(biāo)準(zhǔn)程序來(lái)進(jìn)行日本血吸蟲DNA序列的蛋白質(zhì)編碼區(qū)的識(shí)別，使得各實(shí)驗(yàn)室所提交的序列的編碼區(qū)識(shí)別出現(xiàn)一些差異，本研究將基于序列內(nèi)部特征的序列譜分析和馬爾科夫模型等方法與基于序列外部特征的方法如編碼區(qū)起始位點(diǎn)和終止位點(diǎn)的識(shí)別等相結(jié)合，即采用多服務(wù)器綜合分析流程，，對(duì)上述樣本序列進(jìn)行了分析。對(duì)116條全長(zhǎng)cDNA序列的預(yù)測(cè)結(jié)果表明，僅有5％的序列(6條)與中國(guó)國(guó)家人類基因組南方研究中心(以下稱南方中心)的預(yù)測(cè)結(jié)果完全不同；有8.6％(及1.7％)的序列的預(yù)測(cè)讀碼框與南方中心預(yù)測(cè)的相同，但長(zhǎng)度短于(及長(zhǎng)于)南方中心注釋結(jié)果；其余預(yù)測(cè)結(jié)果與南方中心注釋的完全相同。對(duì)71條EST序列組裝后得到非冗余的51條EST序列，成功地用上述流程對(duì)其進(jìn)行了蛋白質(zhì)編碼區(qū)的識(shí)別。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
【學(xué)位授予單位】：上海師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392

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