Subramanian Nirmala, Chinnappan Sudandiradoss
Bioinformatics Division, School of Biosciences and Technology, VIT University, Vellore, India.
Asian Pac J Cancer Prev. 2013;14(7):4167-75. doi: 10.7314/apjcp.2013.14.7.4167.
A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, EpiJen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.
宫颈癌研究当前面临的一个主要挑战和限制是针对人乳头瘤病毒(HPV)表位开发疫苗。尽管针对HPV的表位鉴定已开展了许多研究,但对于被认为会引发宫颈癌的高危型HPV,尚未进行过计算方面的工作。在所有高危型HPV中,HPV 16、HPV 18和HPV 45导致了全球94%的女性宫颈癌。在这项工作中,我们通过计算预测了高危型HPV的E6蛋白中的多聚表位。我们确定了保守残基、HLA I类、HLA II类和B细胞表位及其相应的二级结构构象。为完成这项任务,我们使用了极为精确的生物信息学工具,如ClustalW2、MAPPP、NetMHC、EpiJen、EpiTop 1.0、ABCpred、BCpred和PSIPred。我们的研究确定了特定区域“FAFR(K)DL”以及随后的“KLPD(Q)LCTEL”片段,这些片段被证明是存在于人白细胞抗原(HLA)I类、II类分子以及B细胞中的多聚表位。这些片段还符合被视为多聚表位的所有合适特征,并得到了先前报道的实验结果的支持证据。因此,我们得出结论,这些区域对于设计针对宫颈癌的特异性治疗疫苗至关重要。