PSEUDOMONAS FLUORESCENS-ENCODED I2-LIKE T CELL ANTIGEN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在人类克罗恩病(CD)和小鼠炎症性肠病(IBD)模型中，共生细菌已成为重要的致病因素。最近有报道称，I2是一个新的微生物起源的基因片段，与人类CD相关，编码一个T细胞超抗原。基因组克隆揭示了一个包含荧光假单胞菌全长I2基因(PfiT)的基因座。CD4+T细胞对重组蛋白的反应对I2和pfiT是有效的。PfiT具有毒力因子的几个特征：与铁反应位点相关，限制物种分布，以及T细胞超抗原生物活性。这些发现提示pfiT和荧光假单胞菌在克罗恩病发病机制中的作用。目前的项目是确定pfit的晶体结构。得到了Se-Met取代的PFT晶体。使用内部X射线系统，最好的晶体衍射率达到1.9A。

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. Commensal bacteria have emerged as an important disease factor in human Crohn's disease (CD) and murine inflammatory bowel disease (IBD) models. it was recently reported that I2, a novel gene segment of microbial origin, is associated with human CD and that encodes a T-cell superantigen. Genomic cloning disclosed a locus containing the full-length I2 gene (pfiT) from Pseudomonas fluorescens. CD4+ T-cell responses to recombinant proteins were potent for I2 and pfiT. pfiT has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for pfiT and P. fluorescens in the pathogenesis of Crohn's disease. The current project is to determine the crystal structure of pfiT. Crystals of Se-Met substituted pfiT have been obtained. The best crystals diffracted to 1.9A resolution using an in-house X-ray system.