Molecular Interactions Of Lymphoid Cell Receptors

这个项目利用了实验室在研究分子相互作用和分子结构方面的专业知识。具体地说，在我们之前对TAPBPR类分子的结构研究的基础上，我们最近确定了多肽负载复合体(PLC)的主要伴侣成分Tapasin与MHC-I分子HLAB*44：05的复合体的X射线晶体结构。这种结构扩展了我们对MHC-I分子如何负载肽的结构细节的了解，由伴侣Tapasin进行的分子构象调整以稳定MHC-I分子的多肽受体构象，以及Tapasin在允许肽交换有利于高亲和力多肽方面所起的催化作用。这些基本的观察结果完善了我们对多肽加载过程的分子理解。除了这些结构研究外，我们还培育了TAPBPR基因敲除小鼠，并正在研究TAPBPR和Tapasin在抗原提呈和交叉提呈过程中的作用。

This project takes advantage of the laboratory's expertise in studying molecular interactions and molecular structure. Specifically, following up on our previous structural studies of the tapasin-like molecule, TAPBPR, we have recently determined the X-ray crystallographic structure of the major chaperone component of the peptide-loading complex (PLC), tapasin, in complex with an MHC-I molecule, HLA-B*44:05. This structure extends our knowledge of the structural details of how MHC-I molecules load with peptides, the molecular conformational adjustments that are made by the chaperone, tapasin, to stabilize a peptide receptive conformation of the MHC-I molecule, and the catalytic role that tapasin plays in allowing peptide exchange favoring high affinity peptides. These fundamental observations refine our molecular understanding the peptide loading process. In addition to these structural studies, we have generated TAPBPR knockout mice and are studying the role of TAPBPR and tapasin in the processes of antigen presentation and cross-presentation.