TUBULOINTERSTITIAL NEPHRITIS BASEMENT MEMBRANE ANTIGENS

肾小管间质性肾炎(TIN)的特征是肾小管上皮细胞 肾小管和间质中单个核细胞和 多形核白细胞。免疫介导型锡有 肾免疫动物模型的研究进展 肾小管基底膜(TBM)和粗肾组织。蜂窝和 体液免疫反应在TIN发病机制中的作用 在这些模型中。虽然免疫病理机制一直是 在模型系统中进行了广泛的研究，对 肾脏成分在疾病过程中的身份和作用。在人类身上， TIN与抗TBM抗体和细胞免疫元件有关 被认为是起主导作用的。 这项研究计划将进一步表征弹道导弹的一个组成部分(TiN 抗原(TA))与人TIN中的抗TBM血清反应并诱导TIN 在老鼠身上。TA分子量形式之间的结构关系 将会被调查。TA的超微结构定位将是 特色化的。TA的细胞结合及其与其他基质的相互作用 将对组件进行研究。TA的蛋白质序列将通过以下方式推导 测序cDNA. 方法包括：柱层析分离蛋白质， 通过电泳法、化学分析法、蛋白质法进行表征 测序和免疫化学分析。单抗将会是 已开发的分子生物学技术，包括筛选cDNAs 将采用文库、聚合酶链式反应、DNA测序和Northern分析等方法。 电子显微镜将用于超微结构的表征 抗体结合及确定TA及其受体的分子性质 与其他分子的相互作用。 申请者的长期目标是阐明 肾脏疾病中细胞外基质成分的特征 肾基底膜成分的结构和功能，以及 确定肾脏基底膜的组成和组织。

Tubulointerstitial nephritis (TIN) is characterized by abnormalities of renal tubules and interstitium with infiltration of mononuclear and polymorphonuclear leukocytes. Immunologically mediated forms of TIN have been investigated in animal models induced by immunization with kidney tubular basement membrane (TBM) and crude kidney tissue. Cellular and humoral immune responses are variably involved in the pathogenesis of TIN in these models. While immunopathological mechanisms have been investigated extensively in model systems, little is understood about the identity and roles of kidney components in the disease process. In man, TIN is associated with anti-TBM antibodies and cellular immune elements are thought to play a predominant role. This research program will further characterize a component of TBM (TIN antigen (TA)) that reacts with anti-TBM sera in human TIN and induces TIN in rats. Structural relationships between molecular weight forms of TA will be investigated. Ultrastructural localization of TA will be characterized. Cell binding of TA and its interaction with other matrix components will be studied. Protein sequence of TA will be deduced by sequencing cDNA. Methods include: protein isolation by column chromatography, characterization by electrophoresis, chemical analysis, protein sequencing and immunochemical assays. Monoclonal antibodies will be developed and molecular biology techniques, including screening of a cDNA library, PCR, DNA sequencing and Northern analysis will be employed. Electron microscopy will be used for ultrastructural characterization of antibody binding and to define molecular properties of TA and its interactions with other molecules. The applicant's long-term objectives are to elucidate roles of extracellular matrix components in renal disease, to characterize structure and functions of renal basement membrane components, and to define composition and organization of basement membranes in the kidney.