本文關(guān)鍵詞：HIV-1gp41上ELDKWA中和表位及單克隆抗體的研究　出處：《清華大學(xué)》2009年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： HIV gp41 單克隆抗體 ELDKWA表位

【摘要】： 位于人免疫缺陷病毒(HIV-1)跨膜蛋白gp41上的ELDKWA表位是重要中和表位,與之結(jié)合的人源單克隆抗體2F5具有廣泛的中和活性。然而,國際期刊論文多次報導(dǎo),通過人工構(gòu)建含有該表位的免疫原,所誘導(dǎo)出表位特異性的單克隆抗體,均未表現(xiàn)出與2F5相同的中和活性。為了揭示其原因,本論文工作圍繞ELDKWA表位及針對該表位的單克隆抗體,繼續(xù)深入研究和探討了單克隆抗體具有的特性。 本研究以gp41上的重要中和表位ELDKWA為靶位點,設(shè)計表位多肽抗原并制備出單克隆抗體。對本實驗室原有的和重新制備的單克隆抗體的研究發(fā)現(xiàn):(1)實驗所用免疫原的設(shè)計影響抗體應(yīng)答的效果,即使是相同表位多肽抗原,誘導(dǎo)出的單克隆抗體與重組表達(dá)的gp41的結(jié)合能力也存在顯著差異;(2)在膜融合實驗中,這些單抗各自表現(xiàn)出不同的抑制活性;(3)體外病毒中和實驗(前期工作)和假病毒中和實驗表明,不同的單抗在中和能力方面存在巨大差異,能夠中和HIV-1 B亞型野毒株92US657的單抗,不能中和通過轉(zhuǎn)染人工構(gòu)建的B亞型假病毒株JRFL,同時,具有假病毒中和活性的單抗,對于野毒株92US657也不具有中和效果。這些研究結(jié)果提示,針對同一表位的單抗,其與抗原的結(jié)合能力、抑制膜融合的能力以及中和能力和中和活性也可能受到病毒株本身序列及抗體空間結(jié)構(gòu)的影響。
[Abstract]:The ELDKWA epitope located on the transmembrane protein gp41 of human immunodeficiency virus (HIV-1) is an important neutralization epitope, with which the human monoclonal antibody 2F5 has extensive neutralization activity. It has been reported many times in international journals that the epitope specific monoclonal antibody induced by artificial construction of the immunogen containing the epitope does not exhibit the same neutralization activity as 2F5. In this paper, the characteristics of ELDKWA epitopes and monoclonal antibodies against them have been studied. In this study, ELDKWA, an important neutralizing epitope on gp41, was used as the target. The epitope peptide antigen was designed and monoclonal antibody was prepared. It was found that the design of immunogen used in the experiment affected the effect of antibody response. Even with the same epitope polypeptide antigen, the binding ability of the induced monoclonal antibody to the recombinant gp41 was significantly different. (2) in the membrane fusion experiment, these McAbs showed different inhibitory activities. In vitro neutralization experiments (previous work) and pseudoviral neutralization experiments showed that there were significant differences in neutralization ability of different McAbs. The McAb of HIV-1 B subtype wild strain 92US657 could not neutralize the constructed virus strain JRFL, and the McAb with pseudovirus-neutralizing activity could not be neutralized. These results suggest that the monoclonal antibody against the same epitope has the ability to bind to the antigen. The ability of inhibiting membrane fusion, neutralization ability and neutralization activity may also be affected by the sequence of virus strain and the space structure of antibody.
【學(xué)位授予單位】：清華大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R392

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本文編號：1362412