IMMUNE REGULATION

描述：（改编自研究者摘要）：一项重要的 非常大的合成组合肽文库的集合，目前 研究者组织提供的数据，将用于识别 对各种临床相关的T细胞克隆特异的肽配体 自身免疫性疾病的动物模型。这项技术已经被用于筛选 数十种已知和未知的人和鼠CD 4+和CD 8 + T细胞克隆 特异性，以鉴定具有宽范围的 这些克隆人的活动。本研究计划的总体目标是 双重的首先，继续进行中的研究与肽模拟的模型 “学术”抗原系统，以获得更好的了解各方面的 免疫调节，包括TCR/肽/MHC分子的某些细节 T细胞反应的激活或抑制中的相互作用， 培养物中的水平、TCR使用和体内免疫原性的要求。一 一个模型抗原系统，鸽子细胞色素c的大组肽，具有 小鼠T细胞克隆型群体的广泛增殖活性 细胞已经产生。重要的是要联系的功能活动， 这些肽序列与肽/MHC中的物理结合性质， TCR/肽/MHC相互作用，共刺激分子的要求和 体外刺激后的细胞因子谱结果。此外还 重要的是将这组肽的功能活性与 活化的细胞数量和体内后的细胞因子应答谱 次免疫其次，这些研究将扩展到临床相关的 自身免疫性疾病的动物模型，以更好地了解T细胞 免疫原性的激活和体内致病性的开始。进一步 这些领域的知识与识别和设计直接相关， 用作肽和拟肽疫苗的抗原的量 癌症和感染性疾病中的免疫应答以及下调免疫应答 自身免疫性疾病的反应。

DESCRIPTION: (Adapted from the Investigator's abstract): A significant collection of very large synthetic combinatorial peptide libraries, currently available at the investigator organization, will be used to identify arrays of peptide ligands specific for T cell clones of clinical relevance in various animal models of autoimmune disease. This technology has been used to screen dozens of human and murine CD4+ and CD8+ T cell clones of known and unknown specificity to identify agonists and antagonists having a broad range of activities on these clones. The overall goals of this research program are two-fold. First, to continue ongoing studies with peptide mimics of a model "academic" antigen system to gain a better understanding of various aspects of immune regulation, including certain details of TCR/peptide/MHC molecular interactions in the activation or inhibition of T cell responses at the clonal level in culture, TCR usage, and requirements for immunogenicity in vivo. A large panel of peptides of a model antigen system, pigeon cytochrome c, having a wide range of proliferative activity for a clonotypic population of murine T cells has been generated. It is important to relate the functional activity of these peptide sequences to physical binding properties in peptide/MHC and TCR/peptide/MHC interactions, requirements for co-stimulation molecules and the cytokine profile consequence following stimulation in vitro. In addition, it is important to relate the functional activity of this panel of peptides to the numbers of cells activated and the cytokine response profiles following in vivo immunization. Secondly, these studies will be extended to clinically relevant animal models of autoimmune disease to better understand the basis for T cell activation in immunogenicity and the onset of pathogenicity in vivo. Further knowledge in these areas is directly relevant to the identification and design of antigens for use as peptide and peptidomimetic vaccines for up-regulating immune responses in cancer and infectious disease and down-regulating immune responses in autoimmune disease.