SCAVENGER RECEPTOR FUNCTION IN CHAPERONE-ELICITED ADAPTIVE IMMUNE RESPONSES

伴侣引发的适应性免疫反应中的清道夫受体功能

• 批准号: 7609878
• 负责人: Brent L Berwin
• 金额: $ 23.29万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609878
• 关键词: Adjuvant; Antigen Presentation Pathway; Bacteria; Biological Assay; Cell Maturation; Cells; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Data; Dendritic Cells; Funding; Grant; Histocompatibility Antigens Class I; Immune response; Immune system; Immunotoxins; Institution; Leukocytes; Malignant neoplasm of ovary; Mediating; Molecular Chaperones; Mus; Peptides; Peritoneal; Recruitment Activity; Research; Research Personnel; Resources; Role; SR-A proteins; Source; United States National Institutes of Health; anticancer research; ovarian neoplasm; particle; programs; receptor function; response; scavenger receptor; tumor; tumor progression; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our research program currently has two main foci: 1) the role of scavenger receptors in mediating leukocyte-driven adaptive immune responses, and 2) the role of leukocytes in ovarian cancer. The first project focuses on how scavenger receptors mediate the uptake of antigenic particles and how peptides derived from these particles then access the MHC class-I antigen presentation pathway and stimulate the hosts immune system. In pursuing this, we are now collaborating with a former COBRE junior investigator, Dr. Harry Higgs, to study how scavenger receptor class-A (SR-A) mediates the phagocytic uptake of bacteria and the endocytic uptake of molecular chaperones and their associated peptides. Our recent data has identified that SR-A is expressed by dendritic cells and contributes to the phagocytic uptake of bacteria by these cells (Amiel et al., Experimental Cell Research, 2007). Regarding chaperones, we are studying how chaperones function as adjuvants to enhance antigenic responses, using chaperone-stimulated dendritic cell maturation as an assay for identifying the underlying mechanisms. For the second project, we are collaborating with a current COBRE junior investigator, Dr. Jose Conejo-Garcia, to investigate scavenger receptors as a way to target tumor-infiltrating leukocytes and thereby therapeutically treat ovarian cancer. An anti-SR-A immunotoxin proved efficacious in depleting murine peritoneal ID8 ovarian tumor-recruited leukocytes and, importantly, leukocyte depletion blocked the ovarian tumor progression (Bak et al., Cancer Research, 2007). All of the above studies were supported by COBRE funding.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的研究项目目前有两个主要焦点：1）清道夫受体在介导白细胞驱动的适应性免疫反应中的作用，以及2）白细胞在卵巢癌中的作用。第一个项目的重点是清道夫受体如何介导抗原颗粒的摄取，以及这些颗粒衍生的肽如何进入MHC I类抗原呈递途径并刺激宿主的免疫系统。为了实现这一目标，我们现在正在与前COBRE初级研究员Harry Higgs博士合作，研究清道夫受体A类（SR-A）如何介导细菌的吞噬摄取和分子伴侣及其相关肽的内吞摄取。我们最近的数据已经确定，SR-A由树突细胞表达，并有助于这些细胞对细菌的吞噬摄取（Amiel等人，Experimental Cell Research，2007）。关于分子伴侣，我们正在研究分子伴侣如何作为佐剂来增强抗原反应，使用分子伴侣刺激的树突状细胞成熟作为鉴定潜在机制的测定。对于第二个项目，我们正在与目前的COBRE初级研究员Jose Conejo-Garcia博士合作，研究清道夫受体作为靶向肿瘤浸润白细胞的一种方法，从而治疗卵巢癌。证明抗SR-A免疫毒素在消耗小鼠腹膜ID 8卵巢肿瘤募集的白细胞中是有效的，并且重要的是，白细胞消耗阻断了卵巢肿瘤的进展（巴克等人，Cancer Research，2007）。上述所有研究都得到了COBRE基金的支持。