ASSEMBLY, INTRACELLULAR TRAFFICKING, AND FUNCTION OF MHC CLASS IB

IB 类 MHC 的组装、细胞内运输和功能

• 批准号: 5200615
• 负责人: J W YEWDELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200615
• 关键词: CD antigens; MHC class I antigen; antigen presentation; beta globulin; cytotoxic T lymphocyte; intracellular transport; membrane transport proteins; protein structure function; protein transport; recombinant virus; surface antigens; tissue /cell culture; vaccinia virus; virus antigen

Classical class I molecules present endogenous peptide antigens for recognition by cytotoxic T lymphocytes, which are transported by a heterodimer encoded by the TAP1 and TAP2 genes. Nonclassical class I (class Ib) molecules, although similar in structure to classical class I molecules, have an unknown function. We are interested in studying the cell biology and biochemistry of the representative murine class Ib molecules, Q7/b and mCD1.1, with the ultimate goal of determining whether nonclassical class I molecules can present viral antigens to cytotoxic T cells. To study these proteins in a variety of tissue culture cell lines in a strictly controlled manner in vitro and in mice we produced vaccinia virus recombinants expressing these proteins. Using these recombinants we found that cell surface expression of both Q7/b and mCD1.1 requires assembly with beta2-microglobulin. Q7/b expression also requires cells to express TAP, while mCD1.1 expression is TAP independent. In collaboration with A. Bendelac (Princeton University) we found the antigen presentation function of mCD1.1 to a unique subset of T cells parallels the requirement for surface expression.

经典的I类分子呈递内源性肽抗原， 通过细胞毒性T淋巴细胞识别，其通过 由TAP 1和TAP 2基因编码的异二聚体。 非经典I类 （Ib类）分子，尽管结构与经典的 I分子，具有未知的功能。 我们有兴趣研究 代表性Ib类鼠的细胞生物学和生物化学 分子，Q7/B和mCD 1.1，最终目标是确定是否 非经典I类分子可将病毒抗原呈递给细胞毒性 T细胞。 为了研究这些蛋白在各种组织培养细胞中的表达， 系在严格控制的方式在体外和小鼠，我们生产 表达这些蛋白质的牛痘病毒重组体。 使用这些 我们发现Q7/B和 mCD1.1需要与β 2-微球蛋白组装。 Q7/B表达也 需要细胞表达TAP，而mCD1.1表达是TAP 独立的 与A合作。普林斯顿大学（Princeton University） 我们发现mCD1.1的抗原呈递功能是一个独特的亚群， 与表面表达的要求平行。