Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2013 May 30;8(5):e65212. doi: 10.1371/journal.pone.0065212. Print 2013.
By gene transfer of HLA-class I restricted T-cell receptors (TCRs) (HLA-I-TCR) into CD8(+) as well as CD4(+) T-cells, both effector T-cells as well as helper T-cells can be generated. Since most HLA-I-TCRs function best in the presence of the CD8 co-receptor, the CD8αß molecule has to be co-transferred into the CD4(+) T-cells to engineer optimal helper T-cells. In this study, we set out to determine the minimal part of CD8αβ needed for optimal co-receptor function in HLA-I-TCR transduced CD4(+) T-cells. For this purpose, we transduced human peripheral blood derived CD4(+) T-cells with several HLA-class I restricted TCRs either with or without co-transfer of different CD8 subunits. We demonstrate that the co-transduced CD8αβ co-receptor in HLA-I-TCR transduced CD4(+) T-cells behaves as an adhesion molecule, since for optimal antigen-specific HLA class I restricted CD4(+) T-cell reactivity the extracellular domains of the CD8α and ß subunits are sufficient.
通过将 HLA 类 I 限制性 T 细胞受体 (TCR)（HLA-I-TCR）基因转移到 CD8(+)和 CD4(+) T 细胞中，可以产生效应 T 细胞和辅助 T 细胞。由于大多数 HLA-I-TCR 在 CD8 共受体存在的情况下功能最佳，因此必须将 CD8αß 分子共转入 CD4(+) T 细胞中，以工程化最佳辅助 T 细胞。在这项研究中，我们着手确定用于 HLA-I-TCR 转导的 CD4(+) T 细胞中最佳共受体功能所需的 CD8αβ 的最小部分。为此，我们用几种 HLA 类 I 限制性 TCR 转导了人外周血来源的 CD4(+) T 细胞，要么共转导不同的 CD8 亚基，要么不共转导。我们证明，在 HLA-I-TCR 转导的 CD4(+) T 细胞中，共转导的 CD8αβ 共受体作为一种粘附分子发挥作用，因为对于最佳的抗原特异性 HLA 类 I 限制性 CD4(+) T 细胞反应，CD8α 和 ß 亚基的细胞外结构域就足够了。
