Enhancement of anti cancer immunity by fusion protein of HSP70 and CD8 T cell epitope from NY-ESO-1

热休克蛋白（HSPs） 70是一个高度保守的分子家族，具有atp酶活性，相对分子质量约为70000 kDa。热休克蛋白伴随抗原肽进入抗原呈递细胞，潜在地允许肽进入MHC I类途径，装载到MHC I类分子上，在那里它们可以被呈递到细胞毒性CD8+ T细胞。反过来，这提供了一种利用从肿瘤中分离出的热休克蛋白和结合肽来免疫癌症的策略。热休克同源蛋白70 （hsc70）通过体外重组与合成肽结合免疫，已被证明可在小鼠体内诱导肽特异性CTL。在这里，我们成功地将hsc70和来自NY-ESO-1的CTL表位融合在一起，NY-ESO-1是睾丸癌抗原之一。我们还发现树突状细胞在喂食融合蛋白后可以将表位呈递到它们的MHC I类上。含有NY-ESO-1肽的Hsc70可通过胞质途径加工，并通过dc呈递给CD8^+ T细胞克隆。这些发现有助于设计和验证Hsc-NY-ESO-1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-1, 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-1 epitope fusion protein.