Evolutionary distance from human homologs reflects allergenicity of animal food proteins
Evolutionary distance from human homologs reflects allergenicity of animal food proteins
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DOI：
10.1016/j.jaci.2007.08.019
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发表时间：
2007-12-01
影响因子：
14.2
通讯作者：
Mills, E. N. Clare
中科院分区：
文献类型：
--
作者：
Jenkins, John A.;Breiteneder, Heimo;Mills, E. N. Clare
背景：变应原的计算机分析可以确定蛋白质序列、结构和变应原性质之间的假定关系。这种系统的分析表明，大多数植物食物过敏原属于有限数量的蛋白质超家族，花粉过敏原的行为相似。目的：我们已经调查了动物食物过敏原的结构关系和它们与人类同源物的进化相关性，以确定一种蛋白质必须与人类的对应物有多接近才能失去其过敏潜力。基于序列同源性的方法将动物食物过敏原分为Pfam家族，并对其进化和结构关系进行了计算机分析。动物性食物过敏原可分为1个主要家族-原肌球蛋白、EF-手蛋白和酪蛋白-以及14个小家族，每个小家族由1至3种过敏原组成。这些过敏原超家族中的每一个的进化关系表明，一般来说，与人类同源物具有约62%以上序列同一性的蛋白质很少是过敏原。在EF-手parvalbumins.Conclusion：这些数据支持的前提下，某些蛋白质结构比其他更过敏原的IgE表位，否则高度保守的区域中的单取代可能会调节allergicity.Conclusion。与植物食物过敏原相比，动物过敏原，如高度保守的原肌球蛋白，挑战人类免疫系统区分外源蛋白和自身蛋白的能力。这样的免疫反应接近成为autoimmune respons.Clinical影响：利用动物过敏原和人类同源物之间的密切关系，在开发重组过敏原用于免疫治疗将需要考虑开发意想不到的自身免疫反应的潜力。
Background: In silico analysis of allergens can identify putative relationships among protein sequence, structure, and allergenic properties. Such systematic analysis reveals that most plant food allergens belong to a restricted number of protein superfamilies, with pollen allergens behaving similarly.Objective: We have investigated the structural relationships of animal food allergens and their evolutionary relatedness to human homologs to define how closely a protein must resemble a human counterpart to lose its allergenic potential.Methods: Profile-based sequence homology methods were used to classify animal food allergens into Pfam families, and in silico analyses of their evolutionary and structural relationships were performed.Results: Animal food allergens could be classified into I main families-tropomyosins, EF-hand proteins, and caseins-along with 14 minor families each composed of I to 3 allergens. The evolutionary relationships of each of these allergen superfamilies; showed that in general, proteins with a sequence identity to a human homolog above approximately 62% were rarely allergenic. Single substitutions in otherwise highly conserved regions containing IgE epitopes in EF-hand parvalbumins may modulate allergenicity.Conclusion: These data support the premise that certain protein structures are more allergenic than others. Contrasting with plant food allergens, animal allergens, such as the highly conserved tropomyosins, challenge the capability of the human immune system to discriminate between foreign and self-proteins. Such immune responses run close to becoming autoimmune responses.Clinical implications: Exploiting the closeness between animal allergens and their human homologs in the development of recombinant allergens for immunotherapy will need to consider the potential for developing unanticipated autoimmune responses.