Nonclassical MHC and Early Thymocyte Development

非经典 MHC 和早期胸腺细胞发育

基本信息

批准号：
7352751
负责人：
Ana S Goyos
金额：
$ 4.4万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7352751
关键词：
Accounting Adopted Adult Amphibia Animals Biological CD8B1 gene Cell Maturation Cell surface Cells Class 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

项目摘要

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.

该提案的总体目标是探索非经典MHC Ib类（Ib类）的参与胸腺细胞分化中的分子。最近变得更加明显的是，在缺乏 MHC 的情况下 la类（la类）表达，可以通过胸腺中的Ib类T细胞进行选择。对此了解不多这种替代胸腺选择过程的生理相关性。我想要检验的假设是在发育、胸腺分化和 T 早期缺乏 Ia 类表达（或低于最佳水平）细胞教育关键取决于 Ib 类。 T细胞的胸腺依赖性及其发挥作用的因素 T 细胞发育调节中的关键作用在有颌脊椎动物中广泛保守。所以，我建议使用青蛙爪蟾及其具有免疫能力但天然缺乏la类的幼虫阶段，作为模型，因为它提供了幼虫早期发育的胸腺在外部可见的优势，易于获取且易于实验操作。重要的是，我们的假设涉及 Ib 类可以在天然缺乏 La 类的情况下进行测试，并且可以在生物环境中研究 T 细胞的发育语境。该提案将为相关的相关问题提供基本的、不受系统发育限制的见解。在个体发育过程中，la 类与 Ib 类介导的胸腺细胞教育途径的贡献。