STRUCTURE AND FUNCTION OF HUMAN SECRETORY COMPONENT

这项研究的目标是评估 上皮细胞对分泌型免疫球蛋白形成的影响 (IG‘s)，它保护身体的粘膜表面。我们的工作 主要研究人类多聚免疫球蛋白受体(PIgR)途径， 它通过上皮细胞运输聚合免疫球蛋白，并 增强它们的分泌功能。最近的研究已经定义了 PIgR及其ITS的蛋白质序列和类Ig结构域结构 裂解产物，分泌成分(SC)，主要 介导聚合物免疫球蛋白转化为 分泌性免疫球蛋白。 使用一组独特的结合到 人SC、分泌型免疫球蛋白A及其胰酶片段 分子，我们已经为这三个分子建立了一个假设模型 PIgR/SC的空间结构及其分子相互作用 该模型提供了一个有用的概念性的 用于设计这些抗体的实验的结构和 用PIgR cDNAs探针检测PIgR与细胞增殖的关系 各种形式的PIgR/SC的结构和功能。 我们将检验以下研究假设：1)倍数 人PIgR和SC的功能是由其结构介导的 这些糖蛋白的特异性Ig样结构域；2)调节 发生在人类猪/干细胞途径的几个位置。我们会 人PIgR和SC结构的生化表征 负责免疫球蛋白结合、转化和蛋白分解的分子 保护。我们的第二个假设将探索潜在的地点 分泌型免疫球蛋白生产的调节或调节 在上皮细胞中。 这些机制在人类中的生理意义将是 被探索。人体体液、组织提取液和薄层 切片、培养细胞和克隆DNA的产品将提供 人体体检补充模型系统 从多个角度探讨PIgR/SC途径。通过刻画 SIG形成的结构和生理要求 人类，并确定可能调节这一点的机制 系统，这些研究应该有助于阐明分子和 粘膜上皮细胞贡献的细胞学基础 豁免权。此信息可能有助于识别 系统中的病理异常与治疗设计 针对黏膜感染的干预措施和/或诊断方法 治疗早期的上皮性恶性肿瘤。

The goal of this study is to evaluate the contribution of the epithelial cell to the formation of secretory immunoglobulins (Ig's), which protect the mucosal surfaces of the body. Our work is focused on the human polymeric Ig receptor (PIgR) pathway, which transports polymeric Ig's across epithelial cells and enchances their secretory function. Recent studies have defined the protein sequence and Ig-like domain structure of PIgR and its cleavage product, secretory component (SC), the primary molecules which mediate the conversion of polymeric Ig into secretory Ig. Using a unique panel of monoclonal antibodies which bind to human SC, secretory IgA and tryptic fragments of these molecules, we have developed a hypothetical model for the three dimensional structure of PIgR/SC and its molecular interactions with the polymeric Ig's. The model provides a useful conceptual structure for designing experiments with these antibodies and PIgR cDNA probes to examine the relationship between the structure and function of the various molecular forms of PIgR/SC. We will test the following research hypotheses: 1) The multiple functions of human PIgR and SC are mediated by the structure of specific Ig-like domains of these glycoproteins; and 2) Modulation occurs at several sites in the human PIg/SC pathway. We will biochemically characterize the structures of human PIgR and SC that are responsible for Ig binding, transcrytosis, and proteolytic protection. Our second hypothesis will explore potential sites for regulation or modulation of secretory immunoglobulin production in epithelial cells. The physiological significance in humans of these mechanisms will be explored. Human biological fluids, tissue extracts and thin sections, cultured cells and products of cloned DNA will provide complementatry model systems for examination of the human PIgR/SC pathway from several perspectives. By characterizing the structural and physiological requirements for SIg formation in humans, and identifying mechanisms which may modulate this system, these studies should help to elucidate the molecular and cellular basis for epithelial cell contributions to mucosal immunity. This information may be useful in identifying pathologic abnormalities in the system and designing therapeutic interventions for mucosal infections and/or diagnostic methods for early epithelial malignancies.