权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Immunodominance in the Human T-cell Responses to Poxvirus and Herpesvirus

人类 T 细胞对痘病毒和疱疹病毒反应的免疫优势

基本信息

批准号：
8243664
负责人：
Jaime M. Calvo-Calle
金额：
$ 33.63万
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：
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/8243664
关键词：
Acquired Immunodeficiency Syndrome Affect Affinity Algorithms Animals Antigen Presentation Antigen Presentation Pathway Antigens Applications Grants Autoimmune Diseases Autophagocytosis Binding Biological Blood specimen CD4 Positive T Lymphocytes CD8B1 gene Categories Cells Cellular Immunity Childhood Clinical Development Dissociation Encephalitis Epitopes Event Failure Family member Fatal Outcome Febrile Convulsions Flow Cytometry Genome Goals Graft Rejection Half-Life Herpesviridae Histocompatibility Antigens Class II Human Human Herpesvirus 6 Immune Immune response Immunity Immunocompromised Host Immunosuppressive Agents Individual Infection Kinetics Location MHC Class I Genes MHC Class II Genes Modeling Molecular Monkeys Pathway interactions Peptide/MHC Complex Peptides Poxviridae Process Proteins Reagent Reporting Research Research Project Grants Resources Role SIV Satellite Viruses Shapes Smallpox Vaccine Specificity T cell response T-Lymphocyte T-Lymphocyte Epitopes Technology Transplantation Vaccines Vaccinia Vaccinia virus Vaccinium Viral Virus Work antigen processing base chemical function computer program insight latent infection particle pathogen protein expression response tool

项目摘要

cell responses are elicited to some but not all possible targets of the immune response, and the rules that govern epitope selection are not completely clear. The main goals of this grant application are first to investigate epitope selection in the human T cell response to pathogens and second to investigate mechanisms of pathogens that affect epitope selection. Vaccinia virus and human herpesvirus 6 will be used as model pathogens. These are large-genome DMA viruses with many potential epitopes for which questions of epitope selection and immune hierarchy are particularly relevant. The proposal has three specific aims. Aim 1 is to determine factors that control epitope selection of the human CD4+ T cell response by using vaccinia virus as a model. Several potential factors affecting epitope selection will be evaluated, including peptide-MHC dissociation kinetics, antigen expression level and location in the infected cell and/or viral particle, and whether the antigen is processed using conventional endosomal processing or autophagy pathways. Aim 2 is to characterize the human CD4+ and CD8+ T cell response to HHV-6 virus. HHV-6 is a relatively recently discovered beta herpesvirus that establishes a long-lasting latent infection, and most people are carriers as a results of childhood exposure. Viral reactivation can occur under immunosuppressive conditions such a post-transplantation therapy or AIDS. Despite the central role of cellular immunity in controlling this virus, very little is known about the T cell response. In work directed at Aim 2, we will characterized the T cell response to HHV-6, study its specificity, and determine if factors important in epitope selection in vaccinia virus also apply to HHV-6. Many viruses have mechanisms to evade or modulate the immune response against them. AIM 3 is to characterize modulation of antigen processing and presentation pathways in vaccinia-infected cells, and to determine whether HHV-6 also has mechanisms to alter antigen processing pathways in infected cells.

细胞反应会引起一些但不是所有可能的免疫反应目标，而规则是