Jenkins John A, Breiteneder Heimo, Mills E N Clare
Institute of Food Research, Norwich, United Kingdom.
J Allergy Clin Immunol. 2007 Dec;120(6):1399-405. doi: 10.1016/j.jaci.2007.08.019. Epub 2007 Nov 1.
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.
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.
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.
Animal food allergens could be classified into 3 main families--tropomyosins, EF-hand proteins, and caseins--along with 14 minor families each composed of 1 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.
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.
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.
对变应原进行计算机分析可确定蛋白质序列、结构和变应原特性之间的假定关系。这种系统分析表明，大多数植物性食物变应原属于数量有限的蛋白质超家族，花粉变应原也表现出类似情况。
我们研究了动物性食物变应原的结构关系及其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对应物有多相似才能失去其变应原潜力。
使用基于谱的序列同源性方法将动物性食物变应原分类到Pfam家族中，并对其进化和结构关系进行计算机分析。
动物性食物变应原可分为3个主要家族——原肌球蛋白、EF手蛋白和酪蛋白——以及14个次要家族，每个次要家族由1至3种变应原组成。这些变应原超家族中每个家族的进化关系表明，一般来说，与人类同源物序列同一性高于约62%的蛋白质很少具有变应原性。EF手型小清蛋白中含有IgE表位的其他高度保守区域中的单个取代可能会调节变应原性。
这些数据支持某些蛋白质结构比其他结构更具变应原性这一前提。与植物性食物变应原不同，动物性变应原，如高度保守的原肌球蛋白，对人类免疫系统区分外来蛋白和自身蛋白的能力提出了挑战。这种免疫反应几乎接近于自身免疫反应。
在开发用于免疫治疗的重组变应原时，利用动物性变应原与其人类同源物之间的相似性将需要考虑发生意外自身免疫反应的可能性。
