TUBULOINTERSTITIAL NEPHRITIS BASEMENT MEMBRANE ANTIGENS

肾小管间质性肾炎（TIN）的特征是 肾小管和肾小管伴单核细胞浸润， 多形性白细胞 免疫介导形式的TIN具有 在肾免疫诱导的动物模型中进行了研究 肾小管基底膜（TBM）和粗肾组织。 蜂窝和 体液免疫应答参与了TIN的发病机制 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。 在人身上， TIN与抗TBM抗体和细胞免疫因子相关 被认为是起主导作用的。 该研究计划将进一步表征TBM的一个组成部分（TIN 抗原（TA）），其与人TIN中的抗TBM血清反应并诱导TIN 对大鼠 TA分子量形式之间的结构关系 将被调查。 TA的超微结构定位 表征了 TA的细胞结合及其与其他基质的相互作用 将对各组成部分进行研究。 TA的蛋白质序列将通过以下推导： 测序cDNA。 方法包括：通过柱层析分离蛋白质， 电泳、化学分析、蛋白质表征 测序和免疫化学测定。 单克隆抗体将是 先进的分子生物学技术，包括筛选cDNA 文库、PCR、DNA测序和北方分析。 电子显微镜将用于超微结构表征 抗体结合，并确定TA的分子特性及其 与其他分子的相互作用。 申请人的长期目标是阐明 肾脏疾病中的细胞外基质成分，以表征 肾基底膜成分的结构和功能， 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.