Application of Heat-shock protein with antigenic peptide for cancer vaccine

热休克蛋白(HSPs)70是一个高度保守的分子家族，具有ATPase活性，相对分子质量约为7万kDa。HSP蛋白伴随抗原肽进入抗原提呈细胞，潜在地允许多肽进入MHC I类途径，加载到MHC I类分子上，在那里它们可以被呈递给细胞毒CD8+T细胞。反过来，这就是。提供了一种利用从肿瘤中分离的热休克蛋白和结合肽进行抗癌免疫的策略。热休克同源蛋白70(Hsc70)通过体外重组与合成肽结合免疫小鼠，可诱导多肽特异性CTL。在这里，我们成功地从基因上融合了hsc70和来自NY ESO-I的.CTL表位，NY ESO-I是癌症-睾丸抗原之一。我们还展示了树突状细胞在喂食融合蛋白后可以将表位呈现在它们的MHC I类分子上。含有NY ESO-1多肽的Hsc70可通过胞浆途径被DC提呈给CD8~+T细胞克隆。这些发现有助于设计和验证使用HSC-NY ESO-L表位融合蛋白的疫苗策略。

Heat shock proteins(HSPs) 70 are a family of highly conserved molecules with ATPase activity and relative molecular masses around 70,000 kDa. Hsp proteins chaperone antigenic peptides into antigen-presenting cells, potentially allowing peptides to enter the MHC class I pathway for loading onto MHC class I molecules, where they can be presented to cytotoxic CD8+ T cells. In turn, this. provides a strategy for immunization against cancer by using hsp and bound peptides that are isolated from tumors. Immunization with heat shock cognate protein 70 (hsc70) bound to synthetic peptides by in vitro reconstitution has been shown to induce peptide-specific CTL in mice. Here, we succeed genetically to fuse hsc70 and a. CTL epitope derived from NY ESO-I, one of the cancer-testis antigens. We also have shown dendritic cell can present, the epitope onto their MHC class I after feeding the fusion protein. Hsc70 with NY ESO-1 peptide can be processed through cytosolic pathway and presented by DCs to CD8^+ T cell clones. These findings help devising and validating vaccine strategies with Hsc-NY ESO-l epitope fusion protein.