Istituto per le Applicazioni del Calcolo "Mauro Picone" - CNR, Rome, Italy.
Department of Biology, University Tor Vergata, Rome, Italy.
PLoS One. 2020 Dec 7;15(12):e0243285. doi: 10.1371/journal.pone.0243285. eCollection 2020.
More than twenty years ago the reverse vaccinology paradigm came to light trying to design new vaccines based on the analysis of genomic information in order to select those pathogen peptides able to trigger an immune response. In this context, focusing on the proteome of Trypanosoma cruzi, we investigated the link between the probabilities for pathogen peptides to be presented on a cell surface and their distance from human self. We found a reasonable but, as far as we know, undiscovered property: the farther the distance between a peptide and the human-self the higher the probability for that peptide to be presented on a cell surface. We also found that the most distant peptides from human self bind, on average, a broader collection of HLAs than expected, implying a potential immunological role in a large portion of individuals. Finally, introducing a novel quantitative indicator for a peptide to measure its potential immunological role, we proposed a pool of peptides that could be potential epitopes and that can be suitable for experimental testing. The software to compute peptide classes according to the distance from human self is free available at http://www.iasi.cnr.it/~dsantoni/nullomers.
二十多年前，反向疫苗学方法问世，试图根据基因组信息分析来设计新疫苗，以便选择能够引发免疫反应的病原体肽。在这种情况下，我们专注于克氏锥虫的蛋白质组，研究了病原体肽在细胞表面呈现的可能性与它们与人类自身的距离之间的联系。我们发现了一个合理但据我们所知尚未被发现的特性：肽与人类自身的距离越远，该肽在细胞表面呈现的可能性就越高。我们还发现，与人类自身距离最远的肽平均结合了更广泛的 HLA 集合，这意味着在很大一部分人群中具有潜在的免疫作用。最后，引入了一种新的定量指标来衡量肽的潜在免疫作用，我们提出了一组可能的表位肽，它们适合进行实验测试。根据与人类自身的距离计算肽类的软件可在 http://www.iasi.cnr.it/~dsantoni/nullomers 免费获得。
