Nonclassical MHC and Early Thymocyte Development

非经典 MHC 和早期胸腺细胞发育

• 批准号: 7064944
• 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
• 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/7064944
• 关键词: MHC class I antigen; T cell receptor; Xenopus; cell differentiation; developmental immunology; gene expression; histocompatibility gene; immunogenetics; in situ hybridization; lymphocyte; nonmammalian vertebrate embryology; northern blottings; polymerase chain reaction; predoctoral investigator; thymus

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本提案的总体目标是探索非经典 MHC Ib 类（Ib 类）分子在胸腺细胞分化中的参与。最近变得更加明显的是，在缺乏MHC Ia类（Ia类）表达的情况下，T细胞可以通过胸腺中的Ib类来选择。关于这种替代性胸腺选择过程的生理相关性知之甚少。我想要测试的假设是，在发育早期缺乏 Ia 类表达（或水平欠佳）的情况下，胸腺分化和 T 细胞教育关键取决于 Ib 类表达。 T 细胞的胸腺依赖性以及在 T 细胞发育调节中起关键作用的因子在有颌脊椎动物中广泛保守。因此，我建议使用青蛙非洲爪蟾及其具有免疫能力但自然类缺陷的幼虫阶段作为模型，因为它具有幼虫早期发育的胸腺在外部可见、易于接近且易于实验操作的优点。重要的是，我们涉及 Ib 类的假设可以在自然缺乏 La 类的情况下进行测试，并且可以在生物学背景下研究 T 细胞的发育。该提案将为个体发育过程中 la 类与 Ib 类介导的胸腺细胞教育途径的相对贡献提供基本的、不受系统发育限制的见解。