The development of a more efficient vaccine is needed to improve tuberculosis control. One of the current approaches is to identify immunogenic T-cell peptides that can elicit a protective and specific immune response. These peptides come from immunogenic proteins of the pathogen. The PE_PGRS33 protein of Mycobacterium tuberculosis has been proved immunogenic. However, little is known about immunogenic T-cell peptides of PE_PGRS33 and their interactions with MHC-II molecules. Therefore, we used the SYFPHEITHI database to determine the immunogenic PE_PGRS33 T-cell peptides. Next, we built homology models by using MOE v2018.1 software in order to obtain information about the specific interactions between the peptides and I-A^k. The AlgPred server was employed to look for allergenic sites in PE_PGRS33. We developed a sequence alignment between PE_PGRS33 and all the human proteins by using BLAST. Three peptides were commercially synthesized, and their activity was evaluated in vitro by the stimulation of PBMC from household contacts of TB patients. Our in silico results showed five immunogenic T-cell peptides. BLAST analysis showed low homology of PE_PGRS33 with human proteins and AlgPred did not reveal allergenic sites in PE_PGRS33. The three peptides triggered the activation of CD4⁺ T cells from the households contacts, showed by the production of IFN-γ. We identified three immunogenic peptides of PE_PGRS33 that demonstrated activity in vitro which allows to deepen into the immune response towards mycobacterial antigens, moving forward to the identification of new vaccine candidates.

需要开发更有效的疫苗来改善结核病的控制。当前的方法之一是鉴定可以引起保护性和特异性免疫应答的免疫原性T细胞肽。这些肽来自病原体的免疫原性蛋白质。结核分枝杆菌的PE_PGRS33蛋白已被证明具有免疫原性。但是，关于PE_PGRS33的免疫原性T细胞肽及其与MHC-II分子的相互作用知之甚少。因此，我们使用SYFPHEITHI数据库来确定具有免疫原性的PE_PGRS33 T细胞肽。接下来，我们使用MOE v2018.1软件建立了同源性模型，以获得有关肽与IA ^k之间特定相互作用的信息。使用AlgPred服务器在PE_PGRS33中查找过敏源位点。我们使用BLAST开发了PE_PGRS33与所有人类蛋白质之间的序列比对。商业合成了三种肽，并通过刺激结核病患者家庭接触PBMC体外评估了它们的活性。我们的计算机分析结果显示了五种免疫原性T细胞肽。BLAST分析显示PE_PGRS33与人蛋白的低同源性，并且AlgPred未揭示PE_PGRS33中的致敏位点。这三种肽触发了来自家庭接触的CD4 ⁺ T细胞的活化，这通过产生IFN-γ来显示。我们鉴定了三种PE_PGRS33免疫原性肽，它们在体外具有活性 它可以加深针对分枝杆菌抗原的免疫反应，从而进一步鉴定新的候选疫苗。