Molecular Interactions Of Lymphoid Cell Receptors

淋巴细胞受体的分子相互作用

• 批准号: 10927746
• 负责人: David Margulies
• 金额: $ 76.58万
• 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/10927746
• 关键词: Adaptive Immune System; Affinity; Antigen Presentation; Antigen Presentation Pathway; Binding; Binding Proteins; Cell Surface Receptors; Complex; Cross Presentation; Cryoelectron Microscopy; Development; Diagnostic; Event; Goals; HLA-B Antigens; Immune; Immune system; Immunologic Receptors; Innate Immune System; Knockout Mice; Knowledge; Laboratories; Ligands; Lymphoid Cell; Molecular; Molecular Chaperones; Molecular Conformation; Molecular Structure; Pathway interactions; Peptides; Play; Process; Receptor Cell; Role; Signal Transduction; Structure; System; Therapeutic; Tumor Antigens; Viral Antigens; X-Ray Crystallography; base; knockout animal; macromolecule; molecular recognition; receptor; tapasin; tool

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.

该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。具体来说，继我们之前对类 Tapasin 分子 TAPBPR 的结构研究之后，我们最近确定了肽负载复合物 (PLC) 的主要伴侣成分 Tapasin 与 MHC 的复合物的 X 射线晶体结构-I分子，HLA-B*44:05。该结构扩展了我们对以下结构细节的了解：MHC-I 分子如何装载肽、由伴侣 Tapasin 进行的分子构象调整，以稳定 MHC-I 分子的肽接受构象，以及催化作用Tapasin 的作用是允许肽交换有利于高亲和力肽。这些基本观察完善了我们对肽加载过程的分子理解。除了这些结构研究之外，我们还培育了 TAPBPR 敲除小鼠，并正在研究 TAPBPR 和 tapasin 在抗原呈递和交叉呈递过程中的作用。

项目成果

Structural aspects of chaperone-mediated peptide loading in the MHC-I antigen presentation pathway.

MHC-I 抗原呈递途径中伴侣介导的肽加载的结构方面。

• DOI: 10.1080/10409238.2019.1610352
• 发表时间: 2019
• 期刊: Critical reviews in biochemistry and molecular biology
• 影响因子: 6.5
• 作者: Natarajan,Kannan;Jiang,Jiansheng;Margulies,DavidH
• 通讯作者: Margulies,DavidH

Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position.

• DOI: 10.4049/jimmunol.0901276
• 发表时间: 2009-08-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Wang R;Natarajan K;Margulies DH
• 通讯作者: Margulies DH

Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor 4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock.

• DOI: 10.1016/j.immuni.2016.05.005
• 发表时间: 2016-06-21
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Voss OH;Murakami Y;Pena MY;Lee HN;Tian L;Margulies DH;Street JM;Yuen PS;Qi CF;Krzewski K;Coligan JE
• 通讯作者: Coligan JE