Nonclassical MHC and Early Thymocyte Development

非经典 MHC 和早期胸腺细胞发育

• 批准号: 7565968
• 负责人: Ana S Goyos
• 金额: $ 2.39万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2009-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7565968
• 关键词: Accounting; Adopted; Adult; Amphibia; Animals; Biological; CD8B1 gene; Cell Maturation; Cell surface; Cells; Complex; Data; Dependence; Dependency; Development; Education; Embryo; Epithelial; Generations; Genes; Gills; Goals; Growth; Immigration; Immune system; Immunity; Immunocompetent; Immunology; Investigation; J segment gene; Jaw; Larva; Ligands; Liver; Lymphocyte; Mammals; Mediating; Modeling; Mus; Organ; Pathway interactions; Pattern; Peptides; Peripheral; Phylogenetic Analysis; Physiological; Play; Process; Publishing; Rana; Regulation; Relative (related person); Reporting; Role; Signal Transduction; Specificity; Spleen; Staging; Surface; System; T-Cell Development; T-Cell Receptor; T-Lymphocyte; TCF Transcription Factor; Testing; Thymocyte Development; Thymocyte Selection; Thymus Gland; Time; Transgenic Model; Transgenic Organisms; Vertebrates; Xenopus; in vivo; insight; novel; receptor; response; thymocyte; transcription factor; xenopus development

The overall goal of this proposal is to explore the involvement of non-classical MHC class Ib (class Ib) molecules in thymocyte differentiation. It has recently become more evident that in the absence of MHC class la (class la) expression, T cells can be selected by class Ib in the thymus. Not much is known about the physiological relevance of this alternative thymic selection process. The hypothesis I aim to test is that in the absence (or suboptimal level) of class la expression early in development, thymic differentiation and T cell education critically depends on class Ib. Both the thymic dependence of T cells and the factors that play key roles in the regulation of T cell development are broadly conserved among jawed vertebrates. Therefore, I propose to use the frog Xenopus and its immunocompetent but naturally class la-deficient larval stage, as a model because it provides the advantage of having the early developing thymus of larvae externally visible, easily accessible and amenable to experimental manipulation. Importantly, our hypothesis involving class Ib can be tested in the natural absence of class la and the development of T cells can be studied in a biological context. This proposal will provide fundamental, and not phylogenetically restricted, insight on the relative contributions of class la versus class Ib-mediated thymocyte education pathways during ontogeny.

本提案的总体目标是探索非经典MHC Ib类（Class Ib）的参与 胸腺细胞分化中的分子。最近越来越明显的是，在没有MHC的情况下， Ia类（Class Ia）表达时，T细胞可以在胸腺中被Ib类选择。没有多少人知道 这种胸腺选择过程的生理相关性。我想验证的假设是， 在发育、胸腺分化和T细胞分化早期缺乏Ia类表达（或亚最佳水平 细胞教育主要依赖于Ib类。T细胞的胸腺依赖性和 在T细胞发育的调节中的关键作用在有颌脊椎动物中是广泛保守的。因此，我们认为， 我建议使用蛙爪蟾和它的免疫活性，但自然类Ia缺陷的幼虫阶段，作为一个 模型，因为它提供了具有外部可见的早期发育的幼虫胸腺的优点， 容易接近并且易于实验操作。重要的是，我们关于Ib类的假设 可以在天然不存在Ia类的情况下进行测试，并且可以在生物学上研究T细胞的发育。 上下文这一建议将提供基本的，而不是遗传学限制，洞察相对 在个体发育期间Ia类与Ib类介导的胸腺细胞教育途径的贡献。