2007 Antigen Cross-Presentation

2007 年抗原交叉展示

基本信息

批准号：
7271580
负责人：
Pramod K. Srivastava
金额：
$ 0.3万
依托单位：
GORDON RESEARCH CONFERENCES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2008-06-30
项目状态：
已结题

项目摘要

The proposal to develop a GRC on Antigen Cross-presentation was borne out of the recognition that science in general has become too reductionist and hyper-specialized. The topic of antigen cross-presentation presents a research area that cuts across several scientific fields, including: Cell Biology; Cell Death; Dendritic Cell Immunobiology; Protein Folding; Lipid Biophysics; Signal Transduction; Antigen Processing and Presentation; and Translational Research including Tumor Immunology, Autoimmunity and Host / Pathogen Interactions. We recognize the need for increased interaction across these fields and see the GRC as an opportunity to build community and forge new collaborative efforts. Background: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune response. They destroy virally infected cells and are considered critical for the eradication of cells on their way toward malignant transformation. To become an effector cell and thus perform these tasks, CTLs must first be activated by an antigen presenting cell (APC) expressing MHC class I / peptide complexes on its cell surface. Classically, only antigen that is synthesized endogenously has access to the MHC I. This presumes direct infection of an APC is a pre-requisite for developing immunity to viruses; and excludes the possibility of generating immunity to tumor-restricted antigens. There is a growing body of evidence, however, which suggests that exogenous antigens can in fact be channeled into the MHC I presentation pathway of an APC for the activation of CTL. This phenomenon has been referred to as ?crosspriming? and the processing of exogenous antigen for MHC I presentation as ?crosspresentation.? The basic science aspects of how this pathway is regulated and the impact of these discoveries on disease pathogenesis and therapy is the focus of our new GRC. Aim: The aim of this conference is to achieve greater scientific interaction between the disciplines implicated in study of antigen cross-presentation. The program will focus on the physiologically relevant mechanisms that account for antigen transfer from non-hematopoetic cells to APCs. Specifically, we will consider heat shock proteins and immune complexes, which act as chaperones for antigen; as well as exosomes and dying cells, which represent efficient ways of packaging antigen for targeted delivery. In addition, we hope to push the envelope by including speakers on topics such as ubiquitination and intracellular transfer of MHC /peptide complexes. In all cases, we attempt to bridge the gap between researchers addressing questions using reductionist model systems with clinicians working at the bedside of patients.

建立抗原交叉呈递 GRC 的提案是基于认识到科学总体上已经变得过于还原论和过度专业化。这抗原交叉呈递主题提出了一个跨越多个科学领域的研究领域领域，包括：细胞生物学；细胞死亡；树突状细胞免疫生物学；蛋白质折叠；脂质生物物理学；信号转导；抗原加工和呈现；和翻译研究包括肿瘤免疫学、自身免疫和宿主/病原体相互作用。我们认识到需要加强这些领域之间的互动，并将 GRC 视为建立社区和开展新的合作努力的机会。背景：细胞毒性T淋巴细胞（CTL）是适应性的重要组成部分。免疫反应。它们破坏病毒感染的细胞，被认为对于消灭正在向恶性转化的细胞。成为效应细胞为了执行这些任务，CTL 必须首先被抗原呈递细胞 (APC) 激活在其细胞表面表达 MHC I 类/肽复合物。传统上，只有抗原内源合成的可以访问 MHC I。这假定 APC 的直接感染是产生病毒免疫力的先决条件；并排除生成的可能性对肿瘤限制性抗原的免疫力。然而，越来越多的证据表明表明外源抗原实际上可以引导至 MHC I 呈递 APC 激活 CTL 的途径。这种现象被称为“交叉引发”。以及 MHC I 呈递的外源抗原的加工称为“交叉呈递”。该途径的调控方式及其影响的基础科学方面这些关于疾病发病机制和治疗的发现是我们新GRC的重点。宗旨：本次会议的目的是加强学术界之间的科学互动。抗原交叉呈递研究涉及的学科。该计划将重点关注解释非造血细胞抗原转移的生理相关机制细胞到 APC。具体来说，我们将考虑热休克蛋白和免疫复合物，它们作为抗原的伴侣；以及外泌体和垂死细胞，它们代表着有效的包装抗原以进行靶向递送的方法。此外，我们希望突破极限包括 MHC/肽的泛素化和细胞内转移等主题的演讲者复合物。在所有情况下，我们都试图弥合研究人员之间的差距使用简化模型系统向在患者床边工作的临床医生提出问题。