ANTIGENIC STRUCTURE OF PURIFIED HOUSE DUST MITE ALLERGEN

屋尘螨(粉尘病)是引起 过敏性疾病，如常年性鼻炎、哮喘和特应性 皮炎和两个主要种类：屋尘虫和屋尘虫。 在美国许多地区的家庭中都发现了粉尘 各州。这个项目的目标是确定主要的 两种主要毒株之间的结构和抗原关系 尘螨变应原组：24kd I组变应原(Der P i， Der f I和Der m I)和15kd II类变应原(Der p II和Der m I DER F II)。这些过敏原的氨基酸序列将是 用多肽测序的组合方法进行测定 (Edman降解和串联质谱学)和 Lambda GT 10的克隆及其结构同源性 过敏原和其他已知氨基酸序列的蛋白质将 比较一下。鼠源性单抗与人的结合 对两组过敏原的免疫球蛋白抗体和免疫球蛋白E抗体进行比较 通过抗原结合放射免疫分析。表位定位研究 将通过比较抗体结合和变性来实现 过敏原、化学修饰的过敏原和多肽片段。 其目的将是确定B细胞表位的谱系， 它们是顺序性的还是拓扑性的，以及哪种氨基酸 残基为抗体结合提供了接触点。小鼠 对I组变应原的抗体反应将在 几个近交系菌株使用不同的免疫制度 调查影响同型的免疫方式 表达也影响表位特异性。人类T细胞 对第一组和第二组过敏原的反应将在#年进行比较 利用尘螨外周血T细胞建立体外细胞培养系统 过敏症患者。合成肽将被用来刺激T细胞 细胞克隆和鉴定T细胞表位。抗原的作用 在将变应原呈递给T细胞之前呈递处理中的细胞 细胞也将被调查。 这项建议提供了一个系统的方法来研究 主要尘螨变应原的分子结构和抗原结构。 这些研究应该有助于更好地理解这些因素。 它们同时影响体液和细胞免疫反应 螨类过敏原。他们还应提供关于以下方面的进一步知识 为什么这些过敏原是鼻炎、哮喘的常见原因 和特应性皮炎。

House dust mites (Dermatophagoides) are an important cause of allergic diseases such as perennial rhinitis, asthma and atopic dermatitis and the two principal species, D. pteronyssinus and D. farinae have been found in homes in many parts of the United States. The aims of this project are to determine the primary structures and the antigenic relationships between the two major groups of dust mite allergens: the 24kd Group I allergens (der p I, Der f I, and Der m I) and the 15kd Group II allergens (Der p II and Der f II). The amino acid sequences of these allergens will be determined using the combined approaches of peptide sequencing (Edman degradation and tandem mass spectrometry) and cDNA cloning in Lambda gt 10. Structural homology between each allergen and other proteins of known amino acid sequence will be compared. Binding of murine monoclonal antibodies and human IgG and IgE antibodies to both allergen groups will be compared by antigen binding radioimmunoassays. Epitope mapping studies will be carried out by comparing antibody binding to denatured allergens, chemically modified allergens and peptide fragments. The aim will be to determine the repertoire of B cell epitopes, whether they are sequential or topographic and which amino acid residues provide the contact points for antibody binding. Murine antibody responses to Group I allergens will be compared in several inbred strains using different immunization regimes to investigate whether modes of immunization which affect isotype expression also influence epitope specificity. Human T cell responses to the Group I and II allergens will be compared n in vitro cell culture systems using peripheral blood T cells from mite allergic patients. Synthetic peptides will be used to stimulate T cell clones and to identify T cell epitopes. The role of antigen presenting cells in processing allergens prior to presentation to T cells will also be investigated. This proposal provides a systematic approach to studying the molecular and antigenic structure of major dust mite allergens. These studies should result in greater understanding of factors which influence both humoral and cellular immune responses to mite allergens. They should also provide further knowledge as to why these allergens are such a common cause of rhinitis, asthma and atopic dermatitis.