Wang X H, Qin Y, Hu M H, Xie Y
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. China.
Cancer Immunol Immunother. 2005 Oct;54(10):971-80. doi: 10.1007/s00262-005-0662-9. Epub 2005 Jun 18.
Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APCs) capable of activating immune responses. Different forms of tumor antigens have been used to load DCs to initiate tumor-specific immune responses. Heat shock proteins (HSPs) are considered natural adjuvants which have the ability to chaperone peptides associated with them presented efficiently by interaction with professional APCs through specific receptors. In the present study, we used HSP, gp96-peptide complexes, derived from human hepatocellular carcinoma (HCC) cells as antigens for pulsing DCs. We found that gp96-peptide complexes derived from HCC cells induced the maturation of DCs by enhancing expression of human leukocyte antigen class II, CD80, CD86, CD40, and CD83. The matured DCs stimulated a high level of autologous T cell proliferation and induced HCC specific cytotoxic T lymphocytes, which specifically killed HCC cells by a major histocompatability complex (MHC) class I restricted mechanism. These findings demonstrate that DCs pulsed with gp96-peptide complexes derived from HCC cells are effective in activating specific T cell responses against HCC cells.
树突状细胞（DCs）是最强大的能够激活免疫反应的抗原呈递细胞（APCs）之一。不同形式的肿瘤抗原已被用于负载DCs以引发肿瘤特异性免疫反应。热休克蛋白（HSPs）被认为是天然佐剂，它们能够通过与专业抗原呈递细胞通过特定受体相互作用，有效地呈递与其相关的伴侣肽。在本研究中，我们使用源自人肝细胞癌（HCC）细胞的HSP、gp96-肽复合物作为脉冲DCs的抗原。我们发现源自HCC细胞的gp96-肽复合物通过增强人类白细胞抗原II类、CD80、CD86、CD40和CD83的表达诱导DCs成熟。成熟的DCs刺激高水平的自体T细胞增殖并诱导HCC特异性细胞毒性T淋巴细胞，其通过主要组织相容性复合体（MHC）I类限制机制特异性杀死HCC细胞。这些发现表明，用源自HCC细胞的gp96-肽复合物脉冲的DCs在激活针对HCC细胞的特异性T细胞反应方面是有效的。
