Redefining the major peanut allergens

描述（由申请人提供）：花生过敏反应的发生是因为易感个体对花生产生异常反应，产生血浆蛋白IgE，该蛋白与肥大细胞和嗜碱性细胞上的IgE高亲和力受体FceRI结合。这种IgE可以与被称为过敏原的特定花生蛋白交联，导致严重的过敏反应。9种花生蛋白已被确定为过敏原，因为它们与过敏个体的IgE结合。其中三种，Ara h1， Ara h2和Ara h3被称为主要的花生过敏原，基于它们在Western blots上结合IgE的能力，在rast抑制试验中与IgE相互作用的能力，以及在体外和/或体内功能试验中具有可测量的活性。根据我们的工作和其他人的工作，我们现在知道Ara h2是这些过敏原中最有效的。我们支持在我们帮助开发的功能分析中根据效力（而不仅仅是活性）来定义主要花生过敏原的概念。我们最新的研究数据表明，对大多数严重花生过敏的患者来说，Ara h2的活性并不是花生致敏活性的主要原因。使用常规色谱结合蛋白质组学，我们已经生成了一个相对较短的新的潜在花生过敏原列表。我们建议通过将我们的功能分析与蛋白质组学的力量相结合，扩大我们的努力，以定量定义主要的花生过敏原。在此过程中，我们将在分子上详细地定义花生过敏原，这些过敏原对花生过敏患者的肥大细胞活化负有最大的责任。我们将在体内用花生过敏小鼠模型测试我们的体外研究结果。这种方法，我们将明确确定花生中最有效的主要过敏原，有可能完全改变我们的想法，即哪些花生过敏原对特定患者的过敏反应最重要。

DESCRIPTION (provided by applicant): Allergic reactions to peanuts occur because susceptible individuals have an aberrant response to peanuts by producing a plasma protein, IgE, that binds to the high affinity receptor for IgE, FceRI, on mast cells and basophils. This IgE can be cross-linked by specific peanut proteins, called allergens, leading to a severe allergic reaction. Nine peanut proteins have been identified as allergens because they bind IgE from allergic individuals. Three of these, Ara h 1, Ara h 2, and Ara h 3 are called the major peanut allergens based on their ability to bind IgE on Western blots, to interact with IgE in RAST-inhibition assays, and to have measurable activity as assessed by in vitro and/or in vivo functional assays. Based on our work and the work of others, we now know that Ara h 2 is the most potent of these allergens. We have championed the concept of defining the major peanut allergens based on potency (not just activity) in functional assays that we have helped to develop. Our newest data examining the allergenicity of peanut extracts that have been specifically depleted of Ara h 2 demonstrate strongly that, for most severely peanut allergic patients, the activity of Ara h 2 does not account for the majority of the allergenic activity of peanuts. Using conventional chromatography combined with proteomics we have generated a relatively short list of new potential peanut allergens. We propose to extend our efforts to define quantitatively the major peanut allergens by combining our functional assays with the power of proteomics. In doing this we will define in molecular detail the peanut allergens most greatly responsible for mast cell activation in peanut allergic patients. We will test our in vitro findings in vivo using a mouse model of peanut allergy. This approach, in which we will definitively identify the most potent major allergens in peanuts has the potential to completely change our thinking as to which peanut allergens are the most important for allergic reactions in specific patients. Public Health Statement: Allergic reactions to peanuts are a major health problem for which current treatments are inadequate. Our knowledge of the molecular basis of peanut allergy is incomplete. This project is designed to use functional assays and proteomics to identify the molecules in peanuts that are most responsible for allergic reactions in susceptible persons.