Guerfali F Z, Ben-Abdallah H, Sghaier R M, Ben-Aissa K, Mkannez G, Attia H, Laouini D
Laboratoire d'Immuno-pathologie, Vaccinologie et Génétique Moléculaire, WHO Collaborating Center for Research and Training in Leishmaniasis, Institut Pasteur de Tunis, 13 place Pasteur, BP 74, Tunis-Belvédère 1002, Tunisia.
Infect Genet Evol. 2009 May;9(3):344-50. doi: 10.1016/j.meegid.2008.02.011. Epub 2008 Mar 4.
It is well established that MHC class II restricted-CD4 T cells are dominant during the development of immunity against Leishmania (L) in the C57BL/6-resistant mouse strain. However and in agreement with a number of previous observations indicating that specific CD8 T cells are primed during natural infection or vaccination in humans, a great deal of evidence obtained recently with the susceptible BALB/c murine model of infection by Leishmania major indicates that CD8 T cells participate in both pathogenesis and immunity to cutaneous leishmaniasis. Our goal herein was to identify in silico all parasitic peptides present in the whole L. major predicted proteome, using several public computational systems for the prediction of peptide binding to all MHC (histocompatibility complex-2) molecules in BALB/c and C57BL/6 mice (Syfpeithi, Rankpep, PRED(BALB/c) and Bimas). Peptides that were predicted to bind to different H2 molecules were then analysed for their homology with any of the murine proteins annotated so far, using the BLAST algorithm. Sets of selected peptides for each H2 molecule were defined by different prediction systems and compared to each other. Surprisingly, the results showed that a higher number of L. major peptides were predicted to bind H2 BALB/c molecules and very few or none to bind H2 C57BL/6 molecules. Our finding illustrates how a hybrid immuno-computational approach may be useful for biologists to target an in silico set of selected proteins to define potential candidate antigens for experimental vaccination with greater accuracy as well as a reduced number of T cell antigens.
众所周知,在C57BL/6抗性小鼠品系中,MHC II类限制性CD4 T细胞在抗利什曼原虫免疫的发展过程中占主导地位。然而,与先前一些观察结果一致,这些观察结果表明在人类自然感染或疫苗接种过程中特定的CD8 T细胞被激活,最近利用易感性BALB/c小鼠感染硕大利什曼原虫的模型获得的大量证据表明,CD8 T细胞参与皮肤利什曼病的发病机制和免疫反应。我们在此的目标是利用几种公共计算系统,通过计算机分析硕大利什曼原虫整个预测蛋白质组中存在的所有寄生肽,以预测肽与BALB/c和C57BL/6小鼠中所有MHC(组织相容性复合体-2)分子的结合情况(Syfpeithi、Rankpep、PRED(BALB/c)和Bimas)。然后,使用BLAST算法分析预测与不同H2分子结合的肽与迄今注释的任何小鼠蛋白质的同源性。由不同预测系统定义每个H2分子的选定肽集,并相互比较。令人惊讶的是,结果表明,预测与H2 BALB/c分子结合的硕大利什曼原虫肽数量更多,而预测与H2 C57BL/6分子结合的肽很少或没有。我们的发现说明了一种混合免疫计算方法如何有助于生物学家以计算机方式靶向一组选定的蛋白质,以更准确地定义潜在的候选抗原用于实验性疫苗接种,并减少T细胞抗原的数量。