Narayan Kedar, Su Katherine W, Chou Chih-Ling, Khoruzhenko Stanislav, Sadegh-Nasseri Scheherazade
Graduate Program in Immunology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Mol Immunol. 2009 Sep;46(15):3157-62. doi: 10.1016/j.molimm.2009.07.001. Epub 2009 Jul 31.
The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a "peptide-receptive" MHC class II conformation (MHC(receptive)) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHC(receptive) and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHC(receptive) in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHC(receptive). The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.
肽编辑蛋白HLA-DM（DM）通过产生一种“肽易结合的”MHC II类构象（MHC（易结合态））来催化抗原呈递细胞内与MHC II类分子结合的肽的交换，肽能轻易地与该构象结合并快速解离。虽然最近的研究揭示了DM识别和效应功能的决定因素，但MHC（易结合态）的性质及其与DM的相互作用仍不清楚。在这里，我们表明在没有肽的情况下，DM诱导但不稳定MHC（易结合态）。我们证明某些超抗体会与DM竞争，并且增加溶剂粘度会抑制DM诱导的肽结合。我们认为DM通过与MHC II类分子短暂且反复地相互作用来介导肽交换，持续产生MHC（易结合态）。因此，随着时间的推移，肽和DM同时存在于环境中对于高效生成特异性肽-MHC II类复合物至关重要。
