首页> 外文期刊>Clinical and experimental allergy : >In silico prediction of Ara h 2 T cell epitopes in peanut-allergic children
【24h】

In silico prediction of Ara h 2 T cell epitopes in peanut-allergic children

机译:花生过敏儿童中Ara h 2 T细胞表位的计算机模拟预测

获取原文
获取原文并翻译 | 示例
           

摘要

Background: Despite the frequency and severity of peanut allergy, the only approved treatment is strict avoidance. Different types of immunotherapy with crude peanut extract are not universally effective and have been associated with relatively high adverse reaction rates. Objective: We sought to determine whether in silico predictive algorithms were useful in identifying candidate peptides for an Ara h 2 peptide-based vaccine using peanut-allergic patients' peripheral blood mononuclear cells (PBMCs) in vitro. A human leucocyte antigen (HLA) distribution analysis was also performed. Methods: Major histocompatibility complex (MHC)-class II-binding peptides were predicted using NetMHCIIpan-2.0 and NetMHCII-2.2 algorithms. PBMCs from 80 peanut-allergic patients were stimulated with overlapping 20-mer Ara h 2 peptides. Cell supernatant cytokine profiles were evaluated by multiplex assays. HLA-DRB1* and HLA-DQB1* typing were performed. Results: Four regions of overlapping sequences induced PBMC proliferation and predominant Th2 cytokine production. HLA genotyping showed 30 different DRB1* allele specificities and eight DQ serological specificities. The in silico analysis revealed similar relevant regions and predicted identical or similar core 9-mer epitopes to those identified in vitro. If relevant peptides, as determined by either in vitro or in silico analysis (15 peptides and 9 core epitopes respectively), were used in a peptide-based vaccine, they would cover virtually all subjects in the cohort studied. Conclusions and Clinical Relevance: Four dominant regions in Ara h 2 have been identified, containing sequences that could serve as potential candidates for peptide-based immunotherapy. MHC-class II-based T cell epitope prediction algorithms for HLA-DR and -DQ loci accurately predicted Ara h 2 T cell epitopes in peanut-allergic subjects, suggesting their potential utility in a peptide-based vaccine design for food allergy.
机译:背景:尽管花生过敏的发生频率和严重程度很高,但唯一被批准的治疗方法是严格避免。用粗花生提取物进行的不同类型的免疫疗法不是普遍有效的,并且已经带来了相对较高的不良反应率。目的:我们试图确定计算机模拟预测算法是否可用于在体外使用花生过敏患者的外周血单个核细胞(PBMC)鉴定基于Ara h 2肽的疫苗的候选肽。还进行了人类白细胞抗原(HLA)分布分析。方法:使用NetMHCIIpan-2.0和NetMHCII-2.2算法预测主要的组织相容性复合体(MHC)II类结合肽。用重叠的20-mer Ara h 2肽刺激来自80位花生过敏患者的PBMC。通过多重测定评估细胞上清细胞因子谱。进行了HLA-DRB1 *和HLA-DQB1 *分型。结果:四个重叠序列区域诱导PBMC增殖和Th2细胞因子的主要产生。 HLA基因分型显示30种不同的DRB1 *等位基因特异性和8种DQ血清学特异性。电子计算机分析揭示了相似的相关区域,并预测了与体外鉴定的那些相同或相似的核心9聚体表位。如果通过体外或计算机分析确定的相关肽(分别为15个肽和9个核心表位)用于基于肽的疫苗中,则它们实际上将覆盖研究对象的所有受试者。结论与临床意义:已经鉴定出Ara h 2中的四个显性区域,其中包含可作为基于肽的免疫疗法的潜在候选者的序列。用于HLA-DR和-DQ基因座的基于MHC II类的T细胞表位预测算法可准确预测花生过敏受试者中的Ara h 2 T细胞表位,表明其在基于肽的食品过敏疫苗设计​​中的潜在效用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号