A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules
A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules
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DOI：
10.1093/emboj/17.11.2971
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发表时间：
1998-06-01
期刊：
影响因子：
11.4
通讯作者：
Hämmerling, GJ
中科院分区：
文献类型：
--
作者：
Kropshofer, H;Vogt, AB;Hämmerling, GJ
在B细胞中，非经典的人类白细胞抗原HLADO(DO)和HLADM(Dm)驻留在溶酶体样细胞器中，在那里它们形成紧密的复合体。DM催化从经典的主要组织相容性复合体(MHC)II类分子中去除不变链衍生的片段多肽，对它们进行伴侣，直到多肽可供加载，并作为多肽编辑。在这里，我们表明DO优先促进MHC II类分子的负载，这些分子依赖于DMI的伴侣活性，并对某些多肽产生积极的影响，而对另一些则产生消极的影响。在酸性隔室中，DO参与DR-DM-DO复合体的生理作用，观察到在溶酶体pH下，DM-DO比单独使用DM更有效地稳定空的II类分子。此外，DO在黑色素瘤细胞系中的表达有利于高稳定性多肽的负载。因此，DO似乎是DM的辅助伴侣，从而控制细胞表面呈现的抗原肽的质量。
In B cells, the non-classical human leukocyte antigens HLA-DO (DO) and HLA-DM (DM) are residents of lysosome-like organelles where they form tight complexes. DM catalyzes the removal of invariant chain-derived CLIP peptides from classical major histocompatibility complex (MHC) class II molecules, chaperones them until peptides are available for loading, and functions as a peptide editor. Here we show that DO preferentially promotes loading of MHC class II molecules that are dependent on the chaperone activity of DMI, and influences editing in a positive way for some peptides and negatively for others. In acidic compartments, DO is engaged in DR-DM-DO complexes whose physiological relevance is indicated by the observation that at lysosomal pH DM-DO stabilizes empty class II molecules more efficiently than DM alone. Moreover, expression of DO in a melanoma cell line favors loading of high-stability peptides. Thus, DO appears to act as a co-chaperone of DM, thereby controlling the quality of antigenic peptides to be presented on the cell surface.