Identification of Hsp90-specific receptor expressed on human dendritic cells and its application for cancer immunothearpy

热休克蛋白（HSPs）-肽复合物在预防性和治疗性免疫方案中引起抗肿瘤反应是公认的。我们已经表明，热休克蛋白90抗原复合物进行受体介导的摄取抗原呈递细胞（APC）与随后的代表性的热休克蛋白相关的肽的MHC I类分子的APC，促进有效的交叉呈递。然而，尚未鉴定出APC上表达的Hsp 90受体。特别是，Hsp 90-抗原复合物的内吞作用的受体仍然未知。在这项研究中，我们已经确定了候选分子的热休克蛋白90受体的表达克隆。虽然这种分子被称为ER驻留蛋白，但我们已经证实了在人树突细胞（DC）上的细胞表面表达。此外，我们证明了这种ER驻留蛋白与外源性Hsp 90相互作用。因此，与其他已知的HSP受体如清道夫受体A（SR-A）、LOX-1和CD 91相比，该分子具有独特的特性。我们正在研究该分子是否参与Hsp 90介导的DC交叉呈递。此外，我们现在正在努力建立针对该分子的mAb，用于靶向DC的抗原用于癌症免疫治疗。

It is well established that heat shock proteins (HSPs)-peptides complexes elicit antitumor responses in prophylactic and therapeutic immunization protocols. We have shown that Hsp90-antigen complexes undergo receptor-mediated uptake by antigen presenting cells (APCs) with subsequent representation of the HSP-associated peptides to MHC class I molecules on APCs, facilitating efficient cross-presentation. However, Hsp90 receptors expressed on APCs have not been identified yet. In particular, receptors for endocytosis of Hsp90-antigen complexes remain unknown. In this study, we have identified the candidate molecule for Hsp90 receptor using a expression cloning. Although this molecule is known as an ER-resident protein, we have confirmed the cell surface expression on human dendriric cells (DC). In addition, we demonstrated that this ER-resident protein interacted with exogenous Hsp90. Thus, this molecule has a unique character compared with other known HSP receptors, such as scavenger receptor A (SR-A), LOX-1 and CD91. We are examining that whether this molecule is involved in Hsp90-mediated cross-presentation by DCs. Furthermore, we are now making an effort to establish a mAb against this molecules for the antigen targeting to DCs for the cancer immunotherapy.