SCAVENGER RECEPTOR FUNCTION IN CHAPERONE-ELICITED ADAPTIVE IMMUNE RESPONSES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的研究计划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，2)白细胞在卵巢癌中的作用。第一个项目关注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多肽如何进入MHC-I类抗原递呈途径并刺激宿主免疫系统。为此，我们现在正与前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吸收以及分子伴侣及其相关多肽的内吞吸收。我们最近的数据已经证实，SR-A由树突状细胞表达，并有助于这些细胞吞噬细菌(Amiel等人，实验细胞研究，2007)。关于伴侣，我们正在研究伴侣如何作为佐剂来增强抗原反应，使用伴侣刺激的树突状细胞成熟作为确定潜在机制的一种检测方法。在第二个项目中，我们正在与目前Cobre的初级研究员Jose Conejo-Garcia博士合作，研究清道夫受体，以此作为靶向肿瘤浸润性白细胞的方法，从而治疗卵巢癌。一种抗SR-A免疫毒素在耗尽小鼠腹膜ID8卵巢肿瘤招募的白细胞方面被证明是有效的，重要的是，白细胞耗尽阻止了卵巢肿瘤的进展(Bak等人，癌症研究，2007年)。上述所有研究都得到了科布雷基金的支持。

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.