Mechanisms of peanut (A. hypogaea) glycan adjuvanticity.

描述（由申请人提供）：本研究计划基于临床观察，即人类遇到的少数潜在过敏原占绝大多数过敏反应。免疫系统的前哨细胞，树突状细胞（DC），在指导和促进对抗原的特异性和持久的免疫反应中起着至关重要的作用。已知许多病原体相关分子可促进对细菌和病毒的有效免疫（Th1免疫）。然而，促进过敏型（Th2免疫）免疫反应的信号很少在分子细节上被表征。一个例外是从寄生虫中发现的某些相关糖结构，已被证明是Th2免疫增强剂的必要和充分条件。这种类型的糖结构在植物、节肢动物（如甲壳类动物、昆虫）和寄生虫中很常见，但在哺乳动物中并不常见。这表明，对这些糖结构的识别可能已经进化到保护人类免受寄生虫感染。识别这些与潜在过敏原相关的结构，可能有助于在某些个体中建立过敏反应。我们的初步数据表明，花生中的糖结构是通过特定受体摄取和激活DC以诱导强Th2免疫所必需的。我们将进一步验证这一假设，并通过测试可溶性花生提取物的组分来确定花生中的活性分子，以激活DC （Aim I）。我们将确定参与花生糖激活DC的受体和机制（Aim II）。我们还将使用我的导师建立的花生过敏小鼠模型（Aim III）来测试这些糖对诱导花生过敏反应的重要性。

DESCRIPTION (provided by applicant): This research proposal is based on the clinical observation that a small number of potential allergens that humans encounter account for the large majority of allergic responses. The immune system's sentinel cells, dendritic cells (DC), play a crucial role instructing and boosting the specific and long-lasting immune response to antigen. Many pathogen-associated molecules are known to promote effective immunity to bacteria and viruses (Th1 immunity). However, few signals that promote allergic-type (Th2 immunity) immune responses have been characterized in molecular detail. An exception to this is certain related sugar structures identified from parasitic worms, which have been shown to be both necessary and sufficient as Th2 immune boosters. Sugar structures of this type are common in plants, arthropods (e.g., crustaceans, insects), and parasitic worms - but not mammals. This suggests that recognition of these sugar structures may have evolved to protect humans against parasitic infections. Recognition of such structures associated with potential allergens, may contribute to the establishment of an allergic response in some individuals. Our preliminary data suggest that sugar structures from peanut are necessary for uptake and activation of DC through specific receptors to induce strong Th2 immunity. We will further test this hypothesis and identify active molecules from peanut by testing fractions of soluble peanut extract for the capacity to activate DC (Aim I). We will identify the receptor(s) and mechanisms involved in DC activation by peanut sugars (Aim II). We will also test the importance of these sugars for the induction of peanut anaphylaxis using a mouse model of peanut allergy established by my mentor (Aim III). Relevance: Allergy to peanut (Arachis hypogaea) tends to be persistent and severe. More than 3 million Americans have peanut and/or tree nut allergy. This project attempts to contribute to our understanding of why peanut allergy is particularly common and persistent. Better understanding of the mechanisms that contribute to the establishment of allergic responses may eventually be used in novel preventative or therapeutic strategies.