Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells
Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells
复制标题
DOI：
10.1007/s00262-011-0995-5
复制
发表时间：
2011-06-01
影响因子：
5.8
通讯作者：
Reinherz, Ellis L.
中科院分区：
文献类型：
--
作者：
Anderson, Karen S.;Zeng, Wanyong;Reinherz, Ellis L.
专职APC，如树突状细胞，通常在体外用于产生对肿瘤抗原特异性的细胞毒性T淋巴细胞。除了树突细胞外，CD 40活化的B细胞和变异的K562白血病细胞可以容易地用核酸转染，用于体外和体内抗原呈递。然而，树突状细胞中免疫蛋白酶体成分的表达可能会阻止肿瘤抗原如Mart 1/MelanA的展示。在这里，我们使用三个靶表位，两个来源于肿瘤抗原[Mart 1（26-34）（M26）和Cyp 1B 1（239-247）（Cyp 239）]，一个来源于甲型流感病毒抗原[FluM 1（58-66）（FluM 58）]，以证明CD 40激活的B细胞，如树突状细胞，处理某些肿瘤抗原的能力有限。相比之下，K562 HLA-A*0201转染子有效地加工并将M26和Cyp 239以及流感FluM 58表位呈递给T细胞。这些结果表明，肿瘤抗原基因转移的靶APC的选择可能受到蛋白酶体组分处理某些肿瘤表位的相对功效的限制。重要的是，K562可以作为人工APC开发，有效地处理M26和Cyp 239表位，并推测，通过扩展，其他相关的肿瘤抗原。
Professional APCs, such as dendritic cells, are routinely used in vitro for the generation of cytotoxic T lymphocytes specific for tumor antigens. In addition to dendritic cells, CD40-activated B cells and variant K562 leukemic cells can be readily transfected with nucleic acids for in vitro and in vivo antigen presentation. However, the expression of immunoproteasome components in dendritic cells may preclude display of tumor antigens such as Mart1/MelanA. Here, we use three target epitopes, two derived from tumor antigens [Mart1(26-34) (M26) and Cyp1B1(239-247) (Cyp239)] and one derived from the influenza A viral antigen [FluM1(58-66) (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens. In contrast, the K562 HLA-A*0201 transfectant efficiently processes and presents M26 and Cyp239 as well as the influenza FluM58 epitopes to T cells. These results demonstrate that the choice of target APC for gene transfer of tumor antigens may be limited by the relative efficacy of proteasome components to process certain tumor epitopes. Importantly, K562 can be exploited as an artificial APC, efficient in processing both M26 and Cyp239 epitopes and presumably, by extension, other relevant tumor antigens.