Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2019 Jan 29;509(1):216-221. doi: 10.1016/j.bbrc.2018.12.106. Epub 2018 Dec 23.
Major histocompatibility complex class II (MHC II) molecules are mainly expressed on antigen presentation cells and play an important role in immune response. It has been reported that MHC II molecules are also detected in serum as a soluble form (sMHC II molecules), and they are considered to be involved in the maintenance of self-tolerance. However, the mechanism by which sMHC II molecules are produced remains unclear. Invariant chain (Ii), also called CD74, plays an important role in antigen presentation of MHC II molecules. In the present study, we analyzed the role of Ii on the production of sMHC II molecules. We found that the amount of sMHC II molecules in serum was decreased in Ii-deficient mice compared to wild-type mice. sMHC II molecules were secreted from cells transfected with MHC II molecules and Ii but not from cells transfected with MHC II molecules alone. Moreover, isoform p41 of Ii-transfected cells induced more sMHC II molecules compared to isoform p31-transfected cells. The molecular weight of sMHC II molecules from MHC II and Ii p41-transfected cells was approximately 60 kDa, indicating that sMHC II molecules are a single heterodimer of α and β chains that is not associated with micro-vesicles. From the analysis of Ii-deletion mutants, we found that the luminal domain of Ii p41 is crucial for the production of sMHC II molecules. These results suggested that Ii has an important role in production of sMHC II molecules.
主要组织相容性复合体 II 类 (MHC II) 分子主要表达于抗原呈递细胞上，在免疫反应中发挥重要作用。据报道，MHC II 分子也以可溶性形式 (sMHC II 分子) 存在于血清中，被认为参与了自身耐受的维持。然而，sMHC II 分子产生的机制尚不清楚。不变链 (Ii)，也称为 CD74，在 MHC II 分子的抗原呈递中发挥重要作用。在本研究中，我们分析了 Ii 在 sMHC II 分子产生中的作用。我们发现，与野生型小鼠相比，Ii 缺陷型小鼠血清中的 sMHC II 分子数量减少。MHC II 分子和 Ii 转染的细胞会分泌 sMHC II 分子，但单独转染 MHC II 分子的细胞则不会。此外，与 p31 转染的细胞相比，p41 转染的 Ii 细胞诱导产生了更多的 sMHC II 分子。来自 MHC II 和 Ii p41 转染细胞的 sMHC II 分子的分子量约为 60kDa，表明 sMHC II 分子是一个与微泡无关的 α 和 β 链的单一异二聚体。通过对 Ii 缺失突变体的分析，我们发现 Ii p41 的腔域对于 sMHC II 分子的产生至关重要。这些结果表明，Ii 在 sMHC II 分子的产生中具有重要作用。
