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Robust T cell stimulation by Epstein-Barr virus-transformed B cells after antigen targeting to DEC-205

机译:抗原靶向DEC-205后,由爱泼斯坦-巴尔病毒转化的B细胞对T细胞的强大刺激

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摘要

DEC-205 is a type I transmembrane multilectin receptor that is predominantly expressed on dendritic cells (DCs). Therefore, previous studies primarily focused on processing of DEC-205–targeted antigens by this potent antigen presenting cell type. Here we show that Epstein-Barr virus (EBV) transformed lymphoblastoid B-cell lines (LCLs) not only express DEC-205 at similar levels to DCs, but also efficiently present targeted EBV nuclear antigen 1 (EBNA1) and EBV-latent membrane protein 1 (LMP1) to EBNA1- and LMP1-specific CD4+ and CD8+ T-cell clones in vitro. Targeting of antigens to DEC-205 on B cells led to more efficient MHC class II than I loading, and stimulated T cells more efficiently than targeting to DEC-205 on DCs. Although LCLs internalized DEC-205–targeted antigens less efficiently than DCs, they retained them for longer time periods and delivered them to endosomal compartments that receive also B-cell receptor targeted proteins. This could facilitate prolonged T-cell stimulation and efficient MHC class II loading, and, indeed, CD4+ T-cell expansion by DEC-205–targeted vaccination was significantly compromised in B-cell deficient mice. These studies suggest that B cells, activated by virus transformation or other means, can contribute to T-cell stimulation after DEC-205 targeting of antigens during vaccination.
机译:DEC-205是主要在树突细胞(DC)上表达的I型跨膜多凝集素受体。因此,以前的研究主要集中在这种有效的抗原呈递细胞类型对DEC-205靶向抗原的加工上。在这里,我们显示爱泼斯坦-巴尔病毒(EBV)转化的淋巴母细胞B细胞系(LCL)不仅以与DC相似的水平表达DEC-205,而且还有效地展示了靶向EBV核抗原1(EBNA1)和EBV潜伏膜蛋白1(LMP1)到EBNA1-和LMP1特异性CD4 +和CD8 + T细胞克隆。将抗原靶向B细胞上的DEC-205导致比I装载更有效的II类MHC,并且比靶向DC上的DEC-205更有效地刺激T细胞。尽管LCLs内化DEC-205靶向抗原的效率不及DCs,但它们将它们保留更长的时间,然后将其递送至内体区室,该区室也接受B细胞受体靶向的蛋白质。这可以促进长时间的T细胞刺激和有效的II类MHC负荷,实际上,在缺乏B细胞的小鼠中,DEC-205靶向疫苗的CD4 + T细胞扩增受到严重损害。这些研究表明,通过病毒转化或其他方式激活的B细胞可在疫苗接种过程中以DEC-205靶向抗原后促进T细胞刺激。

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