Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Immunity. 2011 Nov 23;35(5):694-704. doi: 10.1016/j.immuni.2011.10.012.
A limited set of T cell receptor (TCR) variable (V) gene segments are used to create a repertoire of TCRs that recognize all major histocompatibility complex (MHC) ligands within a species. How individual αβTCRs are constructed to specifically recognize a limited set of MHC ligands is unclear. Here we have identified a role for the differential pairing of particular V gene segments in creating TCRs that recognized MHC class II ligands exclusively, or cross-reacted with classical and nonclassical MHC class I ligands. Biophysical and structural experiments indicated that TCR specificity for MHC ligands is not driven by germline-encoded pairwise interactions.Rather, identical TCRβ chains can have altered peptide-MHC (pMHC) binding modes when paired with different TCRα chains. The ability of TCR chain pairing to modify how V region residues interact with pMHC helps to explain how the same V genes are used to create TCRs specific for unique MHC ligands.
有限的一组 T 细胞受体 (TCR) 可变 (V) 基因片段被用于创建 TCR 库，以识别同种内所有主要组织相容性复合体 (MHC) 配体。单个 αβTCR 如何构建以特异性识别有限数量的 MHC 配体尚不清楚。在这里，我们确定了特定 V 基因片段的差异配对在创建专门识别 MHC Ⅱ类配体的 TCR 或与经典和非经典 MHC Ⅰ类配体发生交叉反应中的作用。生物物理和结构实验表明，TCR 对 MHC 配体的特异性不是由胚系编码的成对相互作用驱动的。相反，当与不同的 TCRα 链配对时，相同的 TCRβ 链可以具有改变的肽-MHC (pMHC) 结合模式。TCR 链配对改变 V 区残基与 pMHC 相互作用的能力有助于解释如何使用相同的 V 基因来创建针对独特 MHC 配体的 TCR。
