Molecular Immunology Section, Division of Immunology and Inflammation, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):E3111-8. doi: 10.1073/pnas.1210882109. Epub 2012 Oct 17.
The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.
αβ T 细胞对 MHC 配体的偏倚被认为是 TCR 的固有特性。同样，CD4 和 CD8 共受体通过在 MHC 配体结合时使 Lck 与 TCR 共定位来促进配体限制。为了确定固有配体偏倚的重要性，体内广泛多样化了 T 细胞受体的胚系互补决定区。我们表明，在胸腺细胞选择和外周 T 细胞激活过程中与 MHC 配体的结合对 TCR 结构施加的约束非常小。这种多功能性更符合机会主义，而不是预定的界面形成模式。通过表达含有 TCR-γ 链胚系互补决定区的杂交 TCR，实验证实了这一假设，该 TCR 能够有效地与 MHC 配体结合。
