Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
Mol Immunol. 2013 Mar;53(3):206-13. doi: 10.1016/j.molimm.2012.08.006. Epub 2012 Sep 1.
Major histocompatibility complex class I (MHC I) molecules play a pivotal role in the immune recognition to intracellular pathogens. A number of important splice variants have already been characterized for these molecules in different species, suggesting their important roles in modulation of immune responses. In this study, we have identified and characterized a novel alternatively spliced form of rhesus macaque MHC IA (designated MHC IA-sv2) that lacks exons coding for the α2 and α3 domains. Despite lacking the α2 and α3 domains, MHC IA-sv2 is targeted to the cell surface, as a 23-kDa glycoprotein that is totally susceptible to endoglycosidase-H digestion and is reduced to 18kDa after deglycosylation with PNGase F. In contrast, the full-length MHC IA reaches the cell surface as a 43-kDa protein of form with complex-type N-glycosylation (endoglycosidase-H resistant). Moreover, we provide evidence here that MHC IA-sv2 can self-associate, forming homodimers, or associate with the fully mature MHC IA molecule, forming a heterodimeric structure in mammalian cells. These data demonstrate that the formation of heterodimers may have some functional implications in the fine tuning of MHC IA-mediated innate and adaptive immune responses.
主要组织相容性复合体 I 类（MHC I）分子在细胞内病原体的免疫识别中起着关键作用。在不同物种中，已经对这些分子的许多重要剪接变体进行了描述，这表明它们在调节免疫反应方面的重要作用。在这项研究中，我们鉴定并表征了恒河猴 MHC IA 的一种新的选择性剪接形式（命名为 MHC IA-sv2），它缺乏编码 α2 和 α3 结构域的外显子。尽管缺乏 α2 和 α3 结构域，MHC IA-sv2 仍能靶向细胞表面，作为一种 23kDa 的糖蛋白，完全易受内切糖苷酶 H 的消化，并在使用 PNGase F 进行糖基化去糖基化后减少到 18kDa。相比之下，全长 MHC IA 作为具有复杂型 N-糖基化（内切糖苷酶 H 抗性）的 43kDa 蛋白形式到达细胞表面。此外，我们在这里提供的证据表明，MHC IA-sv2 可以自我缔合，形成同源二聚体，或与完全成熟的 MHC IA 分子结合，在哺乳动物细胞中形成异二聚体结构。这些数据表明，异二聚体的形成可能对 MHC IA 介导的先天和适应性免疫反应的精细调节具有某些功能意义。
