HLA-DM INDUCES CLIP DISSOCIATION FROM MHC CLASS-II ALPHA-BETA DIMERS AND FACILITATES PEPTIDE LOADING
HLA-DM INDUCES CLIP DISSOCIATION FROM MHC CLASS-II ALPHA-BETA DIMERS AND FACILITATES PEPTIDE LOADING
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DOI：
10.1016/0092-8674(95)90061-6
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发表时间：
1995-07-14
期刊：
影响因子：
64.5
通讯作者：
CRESSWELL, P
中科院分区：
文献类型：
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作者：
DENZIN, LK;CRESSWELL, P
人类白细胞抗原DM（HLA-DM）分子在结构上与经典的MHC II类分子相关，并且存在于溶酶体样区室中，其中II类限制性抗原加工被认为发生。缺乏HLA-DM的突变细胞系在抗原加工中有缺陷，并积累与一组嵌套的不变链衍生肽（II类相关不变链肽，CLIP）相关的II类分子。在这里，我们表明，HLA-DM催化解离的CLIP从MHC II类-CLIP复合物在体外，并促进抗原肽的结合。该反应具有酸性pH最佳值，与其在体内溶酶体样隔室中的发生一致。抗体阻断实验表明，需要HLA-DM和MHC II类-CLIP复合物之间的瞬时相互作用。
Human leukocyte antigen DM (HLA-DM) molecules are structurally related to classical MHC class II molecules and reside in the lysosome-like compartment where class II-restricted antigen processing is thought to occur. Mutant cell lines lacking HLA-DM are defective in antigen processing and accumulate class II molecules associated with a nested set of invariant chain-derived peptides (class II-associated invariant chain peptides, CLIP). Here we show that HLA-DM catalyzes the dissociation of CLIP from MHC class II-CLIP complexes in vitro and facilitates the binding of antigenic peptides. The reaction has an acidic pH optimum, consistent with its occurrence in a lysosome-like compartment in vivo. Antibody blocking experiments suggest that a transient interaction between HLA-DM and the MHC class II-CLIP complex is required.