IDENTIFYING T CELL LIGANDS IN SARCOIDOSIS

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。子项目和 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。 结节病是一种病因不明的全身性疾病，90%以上的病例累及肺部。 这种疾病的特征在于活化的CD 4 + T细胞在肺和其他疾病活动部位的积累，并且证据强烈表明这些T细胞密切参与结节病的发展。 这些CD 4 + T细胞在其表面上表达独特的受体，称为T细胞受体（TCR），其识别特定的肽抗原。 这些T细胞表达大约107种不同的TCR，从而产生不同的T细胞库，并允许身体识别和产生对不同数量抗原的免疫应答。 在结节病中，已经显示具有特定TCR（例如Va2.3）的表达增加的肺CD 4 + T细胞。 具有扩张支气管肺泡灌洗（BAL）Va2.3亚群的个体通常表达HLA-DR等位基因DRB 1 *0301。 这些扩张仅存在于肺部，并随着疾病缓解而消失，加强了它们在疾病过程中的重要性。 使用BAL T细胞克隆的一个困难是这些细胞在死亡前只能在培养中扩增很短的时间。 在这项提案中，我们将招募表达DRB 1 *0301和TCR Va2.3 BAL扩增的活动性结节病患者，并使用一种新的方法来定义结节病中的T细胞配体。 这种新的方法将产生“模拟表位”，它可以对已知的肽/蛋白质序列进行筛选，并将提供新的见解的病因结节病抗原。

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. Sarcoidosis is a systemic disorder of unknown etiology which affects the lung in greater than 90% of cases. This disease is characterized by an accumulation of activated CD4+ T cells in the lung and other sites of disease activity, and evidence strongly suggests that these T cells are intimately involved in the development of sarcoidosis. These CD4+ T cells express a unique receptor on their surface, known as the T cell receptor (TCR), that recognizes a specific peptide antigen. There are approximately 107 different TCRs expressed by these T cells, thus generating a diverse T cell repertoire and allowing the body to recognize and generate an immune response to a diverse number of antigens. In sarcoidosis, lung CD4+ T cells with increased expression of particular TCRs, for example Va2.3, have been shown. Individuals with expanded bronchoalveolar lavage (BAL) Va2.3 subsets usually express the HLA-DR allele, DRB1*0301. These expansions are only present in the lung and disappear with disease remission, reinforcing their importance in the disease process. One difficulty in working with BAL T cell clones is that these cells can be expanded in culture for only a short period of time before dying. In this proposal, we will enroll active sarcoidosis patients expressing both DRB1*0301 and TCR Va2.3 BAL expansions and use a novel approach to define the T cell ligands in sarcoidosis. This novel approach will generate "mimotopes" which can be screened against known peptide/protein sequences and will provide new insight into the etiologic sarcoidosis antigen.