Defining putative T cell epitopes from PE and PPE families of proteins of Mycobacterium tuberculosis with vaccine potential
Defining putative T cell epitopes from PE and PPE families of proteins of Mycobacterium tuberculosis with vaccine potential
复制标题
DOI：
10.1016/j.vaccine.2004.08.046
复制
发表时间：
2005-01-26
期刊：
影响因子：
5.5
通讯作者：
Nayak, R
中科院分区：
文献类型：
--
作者：
Chaitra, MG;Hariharaputran, S;Nayak, R
从结核分枝杆菌的免疫相关抗原中鉴定T细胞表位是开发覆盖不同人群的疫苗的关键步骤。PE-PGRS和PPE两个多基因家族约占结核分枝杆菌基因组的10%。然而，由这些大量基因编码的蛋白质的功能是未知的。对PE和PPE蛋白中所有可能的非美聚肽序列进行了计算机分析，以确定它们与33个I类HLA等位基因的结合能力。这些结果表明，在所有的PE和PPE蛋白中，无论蛋白的长度如何，这些肽都被预测为高亲和力的HLA结合物。通过与人类蛋白质组的比较研究，消除了宿主体内可能表现为自性或部分自性肽的病原体肽，从而减少了用于分析的肽的数量。通过分子模型分析了预测的HLA分子识别非命名的结构基础。结构分析结果与结合预测结果具有良好的相关性。该分析还导致了对肽与I类HLA不同等位基因的结合谱的理解。预测的表位可以通过实验测试，以确定它们是否包含在HLA单倍型特异性结核病的潜在疫苗中。(C) 2004 Elsevier Ltd.版权所有。
The identification of T cell epitopes from immune relevant antigens of Mycobacterium tuberculosis is a critical step in the development of a vaccine covering diverse populations. Two multigene families, PE-PGRS and PPE make up about 10% of the M. tuberculosis genome. However, the functions of the proteins coded by these large numbers of genes are unknown. All possible nonameric peptide sequences from PE and PPE proteins were analysed in silico for their ability to bind to 33 alleles of class I HLA. These results reveal that of all PE and PPE proteins, a significant number of these peptides are predicted to be high-affinity HLA binders, irrespective of the length of the protein. The pathogen peptides that could behave as self or partially self-peptides in the host were eliminated using a comparative study with human proteome, thus reducing the number of peptides for analysis. The structural basis for recognition of the nonamers by the respective HLA molecules thus predicted was analyzed by molecular modeling. The structural analysis showed good correlation with the binding prediction. The analysis also led to an understanding of the binding profile of the peptides with respect to different alleles of class I HLA. The predicted epitopes can be tested experimentally for their inclusion in a potential vaccine against tuberculosis that is HLA haplotype-specific. (C) 2004 Elsevier Ltd. All rights reserved.