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保护性HIV-1细胞毒性T淋巴细胞(CTL)表位及相应的HLA I类等位基因的鉴定:迈向设计基于CTL的HIV-1疫苗的一步。

Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine.

作者信息

Chakraborty Sajib, Rahman Taibur, Chakravorty Rajib

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Dhaka, Dhaka 1000, Bangladesh.

Department of EEE, University of Melbourne, National ICT Australia, Melbourne, VIC 3010, Australia.

出版信息

Adv Virol. 2014;2014:321974. doi: 10.1155/2014/321974. Epub 2014 Mar 18.

Abstract

Human immunodeficiency virus (HIV) possesses a major threat to the human life largely due to the unavailability of an efficacious vaccine and poor access to the antiretroviral drugs against this deadly virus. High mutation rate in the viral genome underlying the antigenic variability of the viral proteome is the major hindrance as far as the antibody based vaccine development is concerned. Although the exact mechanism by which CTL epitopes and the restricting HLA alleles mediate their action towards slow disease progression is still not clear, the important CTL restricted epitopes for controlling viral infections can be utilized in future vaccine design. This study was designed for the characterization the HIV-1 optimal CTL epitopes and their corresponding HLA alleles. CTL epitope cluster distribution analysis revealed only two HIV-1 proteins, namely, Nef and Gag, which have significant cluster forming capacity. We have found the role of specific HLA supertypes such as HLA B∗07, HLA B∗58, and HLA A∗03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins, to be presented as epitopes. The analyses revealed that the clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially serve as a source of vaccine.

摘要

人类免疫缺陷病毒(HIV)对人类生命构成重大威胁,这主要是因为缺乏有效的疫苗,且难以获得针对这种致命病毒的抗逆转录病毒药物。就基于抗体的疫苗开发而言,病毒基因组的高突变率导致病毒蛋白质组的抗原变异性,这是主要障碍。尽管CTL表位和限制性HLA等位基因介导其对疾病缓慢进展作用的确切机制仍不清楚,但控制病毒感染的重要CTL限制性表位可用于未来的疫苗设计。本研究旨在鉴定HIV-1最佳CTL表位及其相应的HLA等位基因。CTL表位簇分布分析显示,只有两种HIV-1蛋白,即Nef和Gag,具有显著的簇形成能力。我们发现特定的HLA超型,如HLA B∗07、HLA B∗58和HLA A∗03,在选择Nef和Gag蛋白内的疏水和保守氨基酸位置作为表位时所起的作用。分析表明,HIV-1的Nef和p24蛋白的最佳表位簇可能作为疫苗来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe2d/3976937/6ec4890b62af/AV2014-321974.001.jpg

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