HSV-1-specific T-cell responses in human sensory ganglia

人类感觉神经节中 HSV-1 特异性 T 细胞反应

基本信息

批准号：
7738784
负责人：
David M Koelle
金额：
$ 18.21万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-23 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7738784
关键词：
Adult Alleles Amino Acids Animal Model Antigen Presentation Antigen Presentation Pathway Antigen-Presenting Cells Antigens Applications Grants Ascaridil Belief Bilateral Biological Assay Brain CD4 Antigens CD4 Positive T Lymphocytes CD8B1 gene Cadaver Cell Line Cells Chronic Chronic Phase Collection Cornea Critiques Cytometry Data Epitopes Exposure to Eye Infections Face Family Ganglia Genes Genetic Transcription Genomic Library Goals Grant Hand Herpes Simplex Virus Protein Vmw65 Herpesvirus 1 Histocompatibility Antigens Class I Hour Human Human Herpesvirus 2 Human Subject Research Immune response Immunocompetent Immunology In Situ In Vitro Infection Interferon Type II Investigation Lesion Licensing Literature Manufacturer Name Manuscripts Mediating Memory Meninges Methodology Methods Molecular Morbidity - disease rate Mus Myxoid cyst Nature Neonatal Neurons Open Reading Frames Organ Perinatal Peripheral Blood Mononuclear Cell Phenotype Population Preparation Production Proteins Proteome Publications Publishing Recombinant Proteins Recombinants Research Research Design Research Proposals Retina Risk Science Screening procedure Sensory Ganglia Side Signal Transduction Simplexvirus Sorting - Cell Movement Specificity Specimen Staging Stretching Structural Protein Structure of trigeminal ganglion Subunit Vaccines Suggestion System T-Lymphocyte TNF gene Testing Text Thymidine Time Tissues Trans-Activators Translating Translations Transplantation VP 16 Vaccine Design Vaccines Vaccinia Vaccinia virus Viral Viral Antigens Virus Work Writing cohort cytokine design disability experience face bone structure follow-up ganglion cell human disease human subject improved interest member microbiological attachment sites mortality neuronal cell body oral tissue pathogen premature programs recombinase research study response selective expression spatial relationship synthetic peptide systems research vaccine candidate vaccine development vector virtual

项目摘要

1R21AI081060-01A1 Koelle, David M. HSV-1 is a significant human pathogen, causing serious infections of the cornea, retina, brain parenchyma, and facial and oral tissues, and also causing perinatal morbidity and mortality. There is no licensed vaccine for HSV-1. The locus of chronic HSV-1 infection is within neurons in sensory ganglia, particularly the trigeminal ganglia (TG) that enervate that face, cornea, and meninges. Animal models of HSV-1 infection have recently proven that the TG is an immunocompetent organ with regard to the presence of ganglia-resident, HSV-1-specific CD8 and CD4 T-cells, and that these cells are functionally important in explant and transplant systems. To study chronic phase TG HSV-1 immunology in the natural host that HSV-1 has been co-evolving with for millions of years, the present application focuses on the TG immune response to HSV-1 in tissue from anonymous human cadavers. The long term goals of the HSV-1 research program are the rational design of an HSV-1 subunit vaccine and an understanding of antigen processing and presentation to HSV-1-specific T-cells in human TG. This grant represents the beginning of a planned sustained focus on HSV-1 immunology. The first Aim is to determine which HSV-1 epitopes and antigens are recognized by HSV-1-specific CD8 T-cells in human HSV-1-infected trigeminal ganglia. We will use a virtual HSV-1 ORFeome and artificial antigen presenting cells to dissect the HSV-1-specific CD8 T-cell response in TG tissues. The second Aim is to determine which HSV-1 epitopes and antigens are recognized by HSV-1-specific CD4 T-cells in human TG tissues. Antigens that contain multiple epitopes within-donor, that are recognized by T-cells from multiple donors, and are recognized by both CD4 and CD8 T-cells, if these are detected, will be rational candidates for HSV-1 subunit or vectored vaccines.

1R21AI081060-01A1 科勒，大卫·M。 HSV-1 是一种重要的人类病原体，可引起角膜、视网膜、大脑的严重感染实质、面部和口腔组织，也导致围产期发病率和死亡率。没有 HSV-1 许可疫苗。慢性 HSV-1 感染的部位位于感觉神经节的神经元内，尤其是三叉神经节（TG），它使面部、角膜和脑膜变得虚弱。动物模型 HSV-1 感染最近证明 TG 是一个具有免疫功能的器官神经节驻留的 HSV-1 特异性 CD8 和 CD4 T 细胞的存在，并且这些细胞在功能上在外植体和移植系统中很重要。研究慢性期 TG HSV-1 免疫学 HSV-1 与 HSV-1 共同进化了数百万年的天然宿主，目前的应用重点匿名人类尸体组织中 TG 对 HSV-1 的免疫反应。长期目标 HSV-1研究计划的重点是合理设计HSV-1亚单位疫苗和了解人类 TG 中抗原加工和 HSV-1 特异性 T 细胞的呈递。这笔补助金代表着计划持续关注 HSV-1 免疫学的开始。第一个目标是确定人类 HSV-1 特异性 CD8 T 细胞识别哪些 HSV-1 表位和抗原 HSV-1 感染的三叉神经节。我们将使用虚拟 HSV-1 ORFeome 和人工抗原呈现细胞来剖析 TG 组织中 HSV-1 特异性 CD8 T 细胞反应。第二个目标是确定人类 HSV-1 特异性 CD4 T 细胞识别哪些 HSV-1 表位和抗原 TG 组织。供体内含有多个表位的抗原，可被来自供体的 T 细胞识别多个供体，并且被 CD4 和 CD8 T 细胞识别，如果检测到这些，将是合理的 HSV-1 亚单位或载体疫苗的候选者。