The CD8αβ heterodimer plays a crucial role in the stabilization between major histocompatibility complex class I molecules (MHC-I) and the T cell receptor (TCR). The interaction between CD8 and MHC-I can be regulated by posttranslational modifications, which are proposed to play an important role in the development of CD8 T cells. One modification that has been proposed to control CD8 coreceptor function is ribosylation. Utilizing NAD+, the ecto-enzyme adenosine diphosphate (ADP) ribosyl transferase 2.2 (ART2.2) catalyzes the addition of ADP-ribosyl groups onto arginine residues of CD8α or β chains and alters the interaction between the MHC and TCR complexes. To date, only interactions between modified CD8 and classical MHC-I (MHC-Ia), have been investigated and the interaction with non-classical MHC (MHC-Ib) has not been explored. Here, we show that ADP-ribosylation of CD8 facilitates the binding of the liver-restricted nonclassical MHC, H2-Q10, independent of the associated TCR or presented peptide, and propose that this highly regulated binding imposes an additional inhibitory leash on the activation of CD8-expressing cells in the presence of NAD+. These findings highlight additional important roles for nonclassical MHC-I in the regulation of immune responses.

中文翻译：

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CD8αβ 异源二聚体的核糖基化允许与非经典的主要组织相容性分子 H2-Q10 结合。

CD8αβ 异源二聚体在主要组织相容性复合体 I 类分子 (MHC-I) 和 T 细胞受体 (TCR) 之间的稳定中起着至关重要的作用。CD8 和 MHC-I 之间的相互作用可以通过翻译后修饰进行调节，这被认为在 CD8 T 细胞的发育中起重要作用。已提出的一种控制 CD8 辅助受体功能的修饰是核糖基化。利用 NAD+，胞外酶二磷酸腺苷 (ADP) 核糖基转移酶 2.2 (ART2.2) 催化 ADP-核糖基团添加到 CD8α 或 β 链的精氨酸残基上，并改变 MHC 和 TCR 复合物之间的相互作用。迄今为止，仅研究了修饰的 CD8 与经典 MHC-I (MHC-Ia) 之间的相互作用，尚未探索与非经典 MHC (MHC-Ib) 之间的相互作用。这里，我们表明 CD8 的 ADP 核糖基化促进了肝脏限制性非经典 MHC H2-Q10 的结合，独立于相关的 TCR 或呈递的肽，并提出这种高度调节的结合对 CD8-在 NAD+ 存在下表达细胞。这些发现突出了非经典 MHC-I 在调节免疫反应中的其他重要作用。