CAREER: Biomolecular Engineering of Antigen Presentation: Development of an Interdisciplinary Research and Education Toolkit

哺乳动物的免疫系统在抵御疾病和其他生物过程方面显示出令人难以置信的力量和灵活性，刺激受控免疫反应的能力可能会给分子医学的许多领域带来革命性的变化。主要组织相容性复合体蛋白（MHC）向T细胞呈递肽抗原是这些免疫反应的核心；mhc肽结合工程将需要对这一现象进行详细和定量的了解。这将需要孜孜不倦地开发研究工具和基础设施，以培养旨在定量分子设计和优化的人员。提出的工作旨在(1)定量研究a相关家族，定量研究II类主要组织相容性复合体蛋白（MHC-II）与相关肽抗原家族结合的动力学和热力学；(2)通过计算结构分析和功能研究阐明肽理化性质与抗原性之间的相关性；(3)开发一种定向进化方法来定制MHC-II肽结合特性；(4)开展研究生和本科生的讲座和实验课程，教授分子生物技术和生物分子工程的最新方法。

The mammalian immune system demonstrates incredible power and flexibility in protection from disease and other organism processes, and the ability to stimulate controlled immune responses could revolutionize many areas of molecular medicine. Peptide antigen presentation to T cells by major histocompatibility complex proteins (MHC) is central to these immune responses; engineering MHC-peptide binding will require a detailed and quantitative understanding of the phenomena. This will require assiduous development of research tools and infrastructure for personnel training aimed at quantitative molecular design and optimization. The proposed work aims to (1) quantitatively study a related family of A related will be studied to quantitatively examine the kinetics and thermodynamics of binding between class II major histocompatibility complex protein (MHC-II) and a family of related peptide antigens; (2) elucidate correlations between peptide physicochemical properties and antigenic properties through computational structure analysis and functional studies; and (3) develop a directed evolution approach to tailoring MHC-II peptide-binding properties; (4) develop a graduate and undergraduate lecture and laboratory courses teaching state-of-art approaches in molecular biotechnology and biomolecular engineering.