The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway.

The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway.
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DOI:
10.1016/j.coi.2011.11.004
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发表时间:
2012-02
影响因子:
7
通讯作者:
Wucherpfennig KW
Wucherpfennig KW
中科院分区:
医学2区
文献类型:
--
作者:
Schulze MS;Wucherpfennig KW

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HLA-DM在MHC II类分子上肽的装载和编辑中起关键作用。最近的数据表明,MHC II类分子与HLA-DM之间的相互作用周期依赖于肽结合沟的占据状态。空的MHC II类分子与HLA-DM形成稳定的复合物,其被高亲和力肽的结合破坏。有趣的是,具有完全接合的肽的MHC II类分子不能与HLA-DM相互作用,并且HLA-DM结合需要肽N-末端从沟中预先解离。MHC I类分子的肽加载过程有显著的相似性,即使它是由不同细胞区室中的一组不同的蛋白质执行的。
HLA-DM serves a critical function in the loading and editing of peptides on MHC class II molecules. Recent data showed that the interaction cycle between MHC class II molecules and HLA-DM is dependent on the occupancy state of the peptide binding groove. Empty MHC class II molecules form stable complexes with HLA-DM, which are disrupted by binding of high-affinity peptide. Interestingly, MHC class II molecules with fully engaged peptides cannot interact with HLA-DM, and prior dissociation of the peptide N-terminus from the groove is required for HLA-DM binding. There are significant similarities to the peptide loading process for MHC class I molecules, even though it is executed by a distinct set of proteins in a different cellular compartment.
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