Department of Biological Sciences, National Creative Research Initiatives Center for Antigen Presentation, Seoul National University, Seoul, Korea.
Traffic. 2011 Jan;12(1):42-55. doi: 10.1111/j.1600-0854.2010.01132.x. Epub 2010 Nov 3.
Major histocompatibility complex class I (MHC-I) molecules bind antigens in the endoplasmic reticulum (ER) and deliver them to the cell surface for immune surveillance of viruses and tumors. Whereas key steps of MHC-I assembly and its acquisition of peptides in the ER are relatively well defined, little is known about how MHC-I molecules leave the ER for cell surface expression. Here, we show that ER export of human classical MHC-I molecules (HLA-A/-B/-C) is regulated by their C-terminal single amino acid, valine or alanine. These amino acids, conserved in nearly all known human MHC-I alleles, serve as the ER export signal by binding to the Sec23/24 complex, a structural component of coat protein complex II (COPII) vesicles that mediate ER-to-Golgi trafficking. Together, our results strongly suggest that ER export of human classical MHC-I molecules can occur via a receptor-mediated process dictated by a highly conserved ER export signal.
主要组织相容性复合体 I 类 (MHC-I) 分子在内质网 (ER) 中结合抗原，并将其递送到细胞表面，以进行病毒和肿瘤的免疫监视。虽然 MHC-I 组装的关键步骤及其在 ER 中获取肽的过程已经相对明确，但对于 MHC-I 分子如何离开 ER 进行细胞表面表达知之甚少。在这里，我们表明人类经典 MHC-I 分子 (HLA-A/-B/-C) 的 ER 输出受其 C 末端单个氨基酸，缬氨酸或丙氨酸调节。这些氨基酸在几乎所有已知的人类 MHC-I 等位基因中都保守，通过与 Sec23/24 复合物结合作为 ER 输出信号，Sec23/24 复合物是衣壳蛋白复合物 II (COPII) 囊泡的结构成分，介导 ER 到高尔基体的运输。总之，我们的研究结果强烈表明，人类经典 MHC-I 分子的 ER 输出可以通过受高度保守的 ER 输出信号控制的受体介导过程发生。
