Hsp60sp, a signal peptide derived from the leader sequence of heat shock protein 60 kDa (Hsp60), is a Qa-1/HLA-E-binding peptide. We previously showed that Hsp60sp-specific CD8⁺ T cells are involved in the immunoregulation of autoimmune diseases by controlling the response of self-reactive lymphocytes. Here, we report that Hsp60sp-specific CD8⁺ T cells killed malignant lymphocytes in vitro independently of transporter associated with antigen processing (TAP) and classical MHC-I expression. Induction of this cytotoxic T lymphocyte (CTL) response in vivo, either by adoptive transfer of in vitro-amplified CTLs or peptide-loaded dendritic cell immunization, resulted in effective control of lymphoid tumors, including TAP- or classical MHC-I-deficient cells. Hsp60sp-specific immune activation combined with programmed cell death protein 1 (PD-1) blocking synergistically restrained mouse lymphoma development. Importantly, Hsp60sp-specific CD8⁺ T cells did not negatively affect normal tissues and cells. Our data suggest that Hsp60sp-based immunotherapy is an inviting strategy to control lymphoid malignancies.

Hsp60sp是源自热休克蛋白60 kDa（Hsp60）的前导序列的信号肽，是Qa-1 / HLA-E结合肽。我们以前表明，Hsp60sp特异性CD8 ⁺ T细胞通过控制自身反应性淋巴细胞的应答参与自身免疫性疾病的免疫调节。在这里，我们报告Hsp60sp特异性CD8 ⁺ T细胞在体外独立于与抗原加工（TAP）和经典MHC-1表达相关的转运蛋白杀死了恶性淋巴细胞。这种细胞毒性T淋巴细胞的诱导（CTL）应答在体内，或者通过过继性转移的在vitro-扩增的CTL或肽加载的树突状细胞免疫可有效控制淋巴样肿瘤，包括TAP或经典MHC-1缺陷细胞。Hsp60sp特异性免疫激活与程序性细胞死亡蛋白1（PD-1）结合可协同抑制小鼠淋巴瘤的发展。重要的是，Hsp60sp特异性CD8 ⁺ T细胞不会对正常组织和细胞产生负面影响。我们的数据表明，基于Hsp60sp的免疫疗法是控制淋巴恶性肿瘤的诱人策略。