ANTI-RIBOSOMAL ANTIBODY STRUCTURE AND FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 查加斯病，由原生动物寄生虫克氏锥虫引起，影响拉丁美洲的1800万至2000万人。这种感染最严重的表现是慢性查加斯心脏病（cChHD）。查加斯心脏病患者的抗体和克氏锥虫核糖体P2 <$$> x蛋白（TcP 2 <$$> x）羧基末端（B细胞表位R13）的单克隆抗体（或mAb）与<$<$x1肾上腺素能受体（<$<$x1-AR）交叉反应。表达了来源于抗R13 mAb 17.2的可变区的两个单链Fv片段（scFv）C5和B7。scFv C5是二聚体，与TcP 2 x结合的亲和力为Kd = 8 nM，而scFv B7是单体，与TcP 2 x结合的亲和力低于scFv C5，Kd = 46 nM。scFv C5与人x1-AR的第二胞外环的亲和常数为10是的本研究旨在阐明C5和B7单克隆抗体识别TcP 2B和b1-AR的结构基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CHAGAS DISEASE, CAUSED by the protozoan parasite Trypanosoma cruzi, affects 18¿¿¿¿¿"20 million people in Latin America. The most severe manifestation of this infection is chronic Chagas heart disease (cChHD). Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2¿¿¿x protein of Trypanosoma cruzi (TcP2¿¿¿x) cross-react with the ¿¿¿x1 adrenergic receptor (¿¿¿x1-AR). Two single-chain Fv fragments (scFv) C5 and B7 derived from the variable regions of the anti-R13 mAb 17.2 were expressed. scFv C5 was a dimer and bound to TcP2¿¿¿x with an affinity of Kd = 8 nM, whereas scFv B7 was monomeric and had less affinity than scFv C5 for TcP2¿¿¿x, Kd = 46 nM. The affinity constant of scFv C5 to the second extracellular loop of the human ¿¿¿x1-AR was of 10 ¿¿¿M. The aim of this study is to elucidate the structural basis of TcP2B and b1-AR recognition by C5 and B7 monoclonal antibody.