Characterization of Human T Cells Against Chlamydia

描述（由申请人提供）：沙眼衣原体（Ct）是世界上最常见的细菌性传播疾病。在大多数感染者中，他们是无症状的。这对妇女造成健康风险，引起盆腔炎和输卵管不孕，对受感染母亲所生的新生儿也是如此。我们的目标是表征感染个体对Ct的人类T细胞免疫反应，目的是鉴定可用于疫苗开发的免疫原性蛋白和肽。我们将确定CD4或CD8 T细胞反应是否可以针对进入MHC I类或II类抗原加工途径或可能进入这些途径的Ct蛋白引起。这些蛋白的特异性肽表位和呈递肽的HLA同种异体将使用表达单一HLA抗原的B淋巴母细胞样细胞系的独特小组来确定。我们的假设是免疫原性蛋白的某些区域将包含CD4和CD8 T细胞的表位簇，正如我们在主要的外膜蛋白MOMP中发现的那样。ct特异性T细胞的功能特征将通过对抗细胞因子、参与细胞毒性的蛋白质和细胞表面分子的抗体来确定。Lysispot等检测将用于确定CTL功能。感染个体血液中的ct特异性T细胞将被列举为MHC I类四聚体和II类四聚体。我们将确定识别Ct抗原的CD8 T细胞是功能性CTL细胞还是在慢性病毒感染中发现的缺乏CTL活性的潜在“耗尽”T细胞。免疫原性表位交叉保护其他Ct物种（如肺炎C.和鹦鹉螺C.）的潜力将通过序列比较来确定。表征人类T细胞对Ct的反应对于了解人类对Ct的免疫和未来的疫苗开发非常重要。

DESCRIPTION (provided by applicant): Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted disease worldwide. In the majority of infected individuals they are asymptomatic. This poses a heath risk for women, causing pelvic inflammation and tubal infertility, and for newborns from infected mothers. Our goal is to characterize the human T cell immune response to Ct in infected individuals with the goal of identifying immunogenic proteins and peptides that could be used for vaccine development. We will determine whether CD4 or CD8 T cell responses can be elicited against Ct proteins that enter the MHC class I or class II antigen processing pathway or are likely to enter those pathways. Specific peptide epitopes from these proteins and the HLA allotypes that present the peptides will be determined using a unique panel of B lymphoblastoid lines expressing single HLA antigens. Our hypothesis is that some regions of immunogenic proteins will contain epitope clusters for both CD4 and CD8 T cells as we found for the major outer membrane protein MOMP. The functional characteristics of the Ct-specific T cells will be determined using antibodies against cytokines, proteins involved in cytotoxicity, and cell surface molecules. Assays such as the Lysispot assay will be used to determine CTL function. Ct-specific T cells in the blood of infected individuals will be enumerated with MHC class I tetramer and class II tetramers. We will determine if the CD8 T cells recognizing Ct antigens are functional CTL cells or potentially "exhausted" T cells lacking CTL activity, which has been found in chronic viral infections. The potential for immunogenic epitopes to cross-protect other Ct species such as C. pneumonia and C. psittaci will be determined by sequence comparisons. Characterizing human T cell responses to Ct is important for understanding immunity to Ct in humans and for future vaccine development.