Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States of America.
Research and Informatics, Virginia Tech, Blacksburg, VA, United States of America.
PLoS One. 2019 Nov 1;14(11):e0222440. doi: 10.1371/journal.pone.0222440. eCollection 2019.
Food allergies are severe immune responses to plant and animal products mediated by immunoglobulin E (IgE). Peanuts (Arachis hypogaea L.) are among the top 15 crops that feed the world. However, peanuts is among the "big eight food allergens", and allergies induced by peanuts are a significant public health problem and a life-threatening concern. Targeted mutation studies in peanuts demonstrate that single residue alterations in these allergen proteins could result in substantial reduction in allergenicity. Knowledge of peanut allergen proteins is confined to the allotetraploid crop and its two progenitors. We explored frequencies and positions of natural mutations in the hyperallergenic homologues Ara h 2 and Ara h 6 in newly generated sequences for 24 Arachis wild species and the crop species, assessed potential mutational impact on allergenicity using immunoblots and structural modeling, and evaluated whether these mutations follow evolutionary trends. We uncovered a wealth of natural mutations, both substitutions and gaps, including the elimination of immunodominant epitopes in some species. These molecular alterations appear to be associated with substantial reductions in allergenicity. The study demonstrated that Ara h 2 and Ara h 6 follow contrasting modes of natural selection and opposing mutational patterns, particularly in epitope regions. Phylogenetic analysis revealed a progressive trend towards immunodominant epitope evolution in Ara h 2. The findings provide valuable insight into the interactions among mutations, protein structure and immune system response, thus presenting a valuable platform for future manipulation of allergens to minimize, treat or eliminate allergenicity. The study strongly encourages exploration of genepools of economically important plants in allergenicity research.
食物过敏是由免疫球蛋白 E（IgE）介导的对植物和动物产品的严重免疫反应。花生（Arachis hypogaea L.）是全球前 15 大农作物之一。然而，花生属于“八大过敏原”之一，由花生引起的过敏是一个重大的公共卫生问题，也是一个危及生命的问题。在花生中的靶向突变研究表明，这些过敏原蛋白中的单个残基改变可能导致致敏性的显著降低。对花生过敏原蛋白的了解仅限于异源四倍体作物及其两个前体。我们在 24 种野生阿月浑子物种和作物物种的新生成序列中探索了超敏同源物 Ara h 2 和 Ara h 6 中的自然突变频率和位置，使用免疫印迹和结构建模评估了潜在的突变对致敏性的影响，并评估了这些突变是否遵循进化趋势。我们发现了大量的自然突变，包括取代和缺失，包括在一些物种中消除免疫显性表位。这些分子改变似乎与致敏性的显著降低有关。该研究表明，Ara h 2 和 Ara h 6 遵循相反的自然选择模式和相反的突变模式，特别是在表位区域。系统发育分析显示 Ara h 2 中免疫显性表位的进化呈渐进趋势。研究结果为突变、蛋白质结构和免疫系统反应之间的相互作用提供了有价值的见解，从而为未来过敏原的操纵提供了一个有价值的平台，以最大限度地减少、治疗或消除致敏性。该研究强烈鼓励在致敏性研究中探索经济上重要植物的基因库。
