Painter Corrie A, Stern Lawrence J
Department of Biochemistry and Molecular Pharmacology and Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655 USA.
Curr Top Biochem Res. 2011;13(2):39-55.
Antigen presentation by class II MHC proteins (MHC-II) is a critical component of the adaptive immune response to foreign pathogens. Our understanding of how antigens are presented has been greatly enhanced by crystallographic studies of MHC-II-peptide complexes, which have shown a canonical extended conformation of peptide antigens within the peptide-binding domain of MHC-II. However, a detailed understanding of the peptide loading process, which is mediated by the accessory molecule HLA-DM (DM), remains unresolved. MHC-II proteins appear to undergo conformational changes during the peptide loading/exchange process that have not been clearly described in a structural context. In the absence of a crystal structure for the DM-MHC-II complex, mutational studies have provided a low resolution understanding as to how these molecules interact. This review will focus on structural and biochemical studies of the MHC-II-peptide interaction, and on studies of the DM-MHC-II interaction, with an emphasis on identifying structural features important for the mechanism of DM mediated peptide catalysis.
II类主要组织相容性复合体蛋白（MHC-II）介导的抗原呈递是对外源病原体适应性免疫反应的关键组成部分。对MHC-II-肽复合物的晶体学研究极大地增进了我们对抗原呈递方式的理解，这些研究显示了MHC-II肽结合域内肽抗原的典型伸展构象。然而，由辅助分子HLA-DM（DM）介导的肽装载过程的详细情况仍未得到解决。MHC-II蛋白在肽装载/交换过程中似乎会发生构象变化，但在结构层面尚未得到清晰描述。由于缺乏DM-MHC-II复合物的晶体结构，突变研究对这些分子如何相互作用提供了低分辨率的认识。本综述将聚焦于MHC-II-肽相互作用的结构和生化研究，以及DM-MHC-II相互作用的研究，重点是确定对DM介导的肽催化机制至关重要的结构特征。
