MOLECULAR GENETIC ANALYSIS OF LYMPHOCYTE FUNCTION

这些研究的目标是了解基本的分子机制 控制免疫反应中的初始识别事件。 作为 这些例子中，我们已经集中在相互作用的MHC类 I分子，与自身或病毒肽复合，与T细胞 受体，或与自然杀伤细胞上的受体，Ly-49。 我们有 为研究这种相互作用开发了模型系统， 纯化的蛋白质分子以及细胞T细胞反应。 过去一年的主要成果包括：1）制定了一个 细菌表达系统，其中三结构域T细胞受体被 生产，保持生物化学和免疫学的完整性， 结合的生物物理参数与生物活性平行 2）证明这种三结构域的实用性 特异性阻断T细胞活化的T细胞受体; 3）精制 精确测量TCR/MHC/肽的方法 相互作用; 4）评估特定肽在 小鼠MHC I类分子H-2Dd与NK细胞的相互作用 Ly-49 A受体。

The goal of these studies is to understand the basic molecular mechanisms that govern the initial recognition events in the immune response. As examples of these, we have focused on the interaction of the MHC class I molecule, complexed with self or viral peptides, with the T cell receptor, or with a receptor on natural killer cells, Ly-49. We have developed model systems for the study of this interaction both with purified protein molecules as well as with cellular T cell responses. Major accomplishments during the past year include: 1) development of a bacterial expression system in which a three domain T cell receptor is produced that maintains biochemical and immunological integrity, and in which biophysical parameters of binding parallel the biological activity of the molecule; 2) demonstration of the utility of such a three domain T cell receptor for specific blocking of T cell activation; 3) refinement of methodologies for the precise measurement of TCR/MHC/peptide interactions; 4) evaluation of the role of specific peptides in the interaction of the mouse MHC class I molecule H-2Dd with the NK cell receptor Ly-49A.