NK cell regulation of immune responses to dengue

NK 细胞调节登革热免疫反应

基本信息

批准号：
8892538
负责人：
ANUJA MATHEW
金额：
$ 3.85万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-16 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8892538
关键词：
Activated Natural Killer Cell Address Antibodies Antigens Antiviral Agents Binding CD8B1 gene Cell Line Cell physiology Cells Cessation of life Chronic Cytolysis Cytomegalovirus Data Dengue Dengue Virus Disease Disease model Effector Cell Epitopes Family Genotype HIV HLA-Bw4 Hepatitis C virus Human Human Papillomavirus Immune response Individual Killer Cells Lead Licensing Ligands MHC Class I Genes Mediating Mus NK Cell Activation NK cell receptor NKB1 Natural Killer Cells Patients Peptides Peripheral Blood Mononuclear Cell Phase Play Production Proteins Regulation Research Rest Role Severity of illness Signal Transduction T-Lymphocyte Epitopes Validation Viral Viral Pathogenesis Virus Diseases Virus Replication arm base cytokine cytotoxicity killer immunoglobulin-like receptor member prevent public health relevance receptor research study response virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): Natural Killer (NK) cells are primary effector cells of the innate immune response and play a critical role in the control of viral replication in several disease models. Depletions or deficiencies of NK cells lead to significantly more severe viral disease and death in both mice and humans. Killer immunoglobulin-like receptors (KIRs) interact with HLA class I ligands and play a central role in the regulation and activation of naturl killer (NK) cells. The interaction between KIRs and their HLA class I ligands can thus have a profound impact on the efficacy of NK cell-mediated control of viral pathogenesis and has been demonstrated for a number of chronic viral infections. Very little is known about the involvement of NK cells in regulating dengue virus infections. We have found that a CD8 T cell epitope on the non-structural protein 1 (NS1) of dengue interacts with a well characterized inhibitory receptor KIR3DL1 on NK cells. In this application, we will use the antigen-specific tetramers and peptides to dissect the interaction with KIR3DL1 and determine how dengue virus modulates the function of this important subset of NK cells. The studies outlined in this application will provide a better understanding of the importance of KIR-MHC class I interactions on NK cells and provide the rationale to target this innate arm of the immune response to control dengue virus replication.

描述（由申请人提供）：自然杀伤（NK）细胞是先天免疫反应的主要效应细胞，在多种疾病模型中的病毒复制控制中发挥着关键作用。NK 细胞的耗竭或缺陷会导致病毒的严重程度显着增加。杀伤性免疫球蛋白样受体 (KIR) 与 HLA I 类配体相互作用，并在自然杀伤 (NK) 细胞的调节和激活中发挥核心作用。因此，KIR 与其 HLA I 类配体之间的相互作用可以对 NK 细胞介导的病毒发病机制控制的功效产生深远的影响，并且已经在许多慢性病毒感染中证明了 NK 细胞参与调节的情况。我们发现登革热非结构蛋白 1 (NS1) 上的 CD8 T 细胞表位与 NK 细胞上特征明确的抑制性受体 KIR3DL1 相互作用。抗原特异性四聚体和肽来剖析与 KIR3DL1 的相互作用，并确定登革热病毒如何调节这一重要 NK 细胞亚群的功能。本申请中概述的研究将有助于更好地理解 KIR-MHC I 类相互作用的重要性。 NK 细胞，并提供了针对免疫反应的先天臂来控制登革热病毒复制的基本原理。