本文關(guān)鍵詞：人源輪狀病毒T細(xì)胞識(shí)別及其小型豬腹瀉模型的建立　出處：《第三軍醫(yī)大學(xué)》2006年博士論文　論文類型：學(xué)位論文

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【摘要】： A組輪狀病毒是造成全世界嬰幼兒嚴(yán)重腹瀉的最主要病原。最新統(tǒng)計(jì)資料表明,全世界5歲以下兒童每年約有1億3千8百萬患輪狀病毒感染,其中約454,000-705,000例死亡(82%的死亡病例發(fā)生在發(fā)展中國家)。目前,輪狀病毒尚無特效治療藥物及安全有效的預(yù)防性疫苗,對(duì)輪狀病毒感染的免疫保護(hù)機(jī)制的進(jìn)一步研究是當(dāng)前研究的重點(diǎn)與難點(diǎn)。 在小鼠輪狀病毒感染模型中的大量研究表明,TCRαβ+/+CD8+T細(xì)胞在抗輪狀病毒原發(fā)感染及再次感染中具有重要作用。研究發(fā)現(xiàn),在無輪狀病毒抗體的情況下,輪狀病毒感染的成年小鼠的CD8+ T細(xì)胞可被動(dòng)保護(hù)乳鼠,并且可介導(dǎo)重癥免疫缺陷小鼠清除慢性輪狀病毒感染;細(xì)胞毒性T淋巴細(xì)胞(cytotoxic T lymphocytes,CTL)缺陷小鼠(β2-microglobulin knockout mice)及其他封閉了CD8+ T細(xì)胞的小鼠清除輪狀病毒感染的時(shí)間延遲1-4天;B細(xì)胞缺陷(J(H)D基因敲除)小鼠可清除輪狀病毒的原發(fā)感染,封閉CD8+ T細(xì)胞后則轉(zhuǎn)為慢性感染;B細(xì)胞缺陷小鼠原發(fā)感染18天后可介導(dǎo)幾乎完全的免疫保護(hù),6周、5個(gè)月及8個(gè)月仍能介導(dǎo)部分的免疫保護(hù),但封閉CD8+T細(xì)胞后,在原發(fā)輪狀病毒感染13天、18天、6周及5個(gè)月再次攻擊則會(huì)轉(zhuǎn)為輪狀病毒慢性感染,而封閉TCRγδ+/+T細(xì)胞幾乎無影響,表明TCRαβ+/+CD8+ T細(xì)胞介導(dǎo)了對(duì)輪狀病毒再次感染的免疫保護(hù)。進(jìn)一步研究顯示,輪狀病毒結(jié)構(gòu)蛋白VP6與VP7是其CTL效應(yīng)的主要靶標(biāo)。VP6是輪狀病毒的組抗原,其含量占輪狀病毒蛋白總量的51%,同組輪狀病毒VP6的氨基酸序列高度保守(87-99%);VP7是輪狀病毒主要的外殼結(jié)構(gòu)蛋白,約占病毒蛋白總量的30%,與此同時(shí), VP7不但可引起極強(qiáng)的CTL效應(yīng),并且與輪狀病毒不同血清型具有完全的交叉反應(yīng)。盡管現(xiàn)已有猴源輪狀病毒SA11(G3)及牛源輪狀病毒UK(G6)的鼠源限制性CTL表位鑒定方面的報(bào)道,但均不能用于人體內(nèi)輪狀病毒感染中CD8+T細(xì)胞的研究。目前,CD8+T細(xì)胞在人體內(nèi)輪狀病毒感染中的地位與作用如何,尚不明了。至今尚未見輪狀病毒HLA-I類限制性CTL表
[Abstract]:Group A rotavirus is the leading cause of severe diarrhea in infants and young children around the world. The latest statistics show that about 138 million of patients with rotavirus infection in children under the age of 5 every year in the world, which killed about 454000-705000 cases (82% of deaths occurring in developing countries). At present, there is no specific treatment for rotavirus and drug the safe and effective preventive vaccine, further research on the immune protection mechanism of rotavirus infection is the key and difficult point in current research.
Show that in mice model of rotavirus infection in a large number of studies, TCR +/+CD8+T of alpha and beta cells in anti rotavirus primary infection and reinfection plays an important role. The study found that in the absence of rotavirus antibody, adult mouse rotavirus infection of CD8+ T cells passively protect suckling mice and may be mediated in SCID mice to remove chronic rotavirus infection; cytotoxic T lymphocyte (cytotoxic T lymphocytes CTL (knockout) mice deficient in beta 2-microglobulin mice) and other closed CD8+ T cells of mice cleared rotavirus infection time delayed 1-4 days; B cell defects (J (H) D gene in addition) mice can remove rotavirus primary infection, CD8+ closed after T cells are converted to chronic infection; B cell deficient mice 18 days after primary infection may be mediated by immune protection, almost 6 weeks, 5 months and 8 months can still mediated Part of the immune protection, but closed after CD8+T cell in the original rotation of coronavirus infection in 13 days, 18 days, 6 weeks and 5 months again attack will become chronic rotavirus infection, and closed TCR gamma delta +/+T cells had almost no effect, suggesting that TCR alpha beta +/+CD8+ T cell mediated immune protection re infection of rotavirus. Further study showed that rotavirus structural protein VP6 and VP7 is the main target of.VP6 is the CTL effect of rotavirus antigen, its content accounted for 51% of the total rotavirus protein, the amino acid sequence of the same group of rotavirus VP6 highly conserved (87-99%); VP7 the shell structure protein of rotavirus mainly, accounting for about 30% of the total protein of the virus, at the same time, VP7 can not only cause CTL effect is very strong, and with different serotypes of rotavirus has completely cross reactivity. Although we have simian rotavirus SA11 (G3) and UK (G6 Yuanlun bovine rotavirus The mouse) restricted CTL epitope identification report, but are not used in the study of CD8+T cells of rotavirus infection in the human body. At present, how to position and function of CD8+T cells in human rotavirus infection, is still unknown. So far there is no rotavirus HLA-I restricted CTL table

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392

【共引文獻(xiàn)】

相關(guān)期刊論文 前7條

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本文編號(hào)：1362101