Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57
Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57
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DOI：
10.1038/ni1288
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发表时间：
2006-01-01
影响因子：
30.5
通讯作者：
Hämmerling, GJ
中科院分区：
文献类型：
--
作者：
Garbi, N;Tanaka, S;Hämmerling, GJ
巯基氧化还原酶ERp 57是主要组织相容性复合体（MHC）I类途径的肽负载复合物的组成部分，但其功能尚不清楚。为了研究其在抗原呈递中的功能，我们产生了ERp 57缺陷小鼠。通过B细胞区室中的特异性缺失防止了由普遍存在的ERp 57缺失引起的子宫内死亡。我们证明ERp 57是招募MHC I类分子进入装载复合物的核心。在ERp 57缺陷细胞中，我们发现MHC I类分子与负载复合物的短暂相互作用。因此，在稳定状态下，装载复合物中存在非常少的MHC I类分子。表面H-2 K（B）-肽的表达和稳定性降低，模型抗原的呈递减少。我们的研究结果表明，ERp 57不影响的MHC I类分子的氧化还原状态，但稳定组装的肽装载复合物所需的一个重要的结构组成部分。
The thiol-oxidoreductase ERp57 is an integral component of the peptide-loading complex of the major histocompatibility complex (MHC) class I pathway, but its function is unknown. To investigate its function in antigen presentation, we generated ERp57-deficient mice. Death in utero caused by ubiquitous ERp57 deletion was prevented by specific deletion in the B cell compartment. We demonstrate that ERp57 was central for recruitment of MHC class I molecules into the loading complex. In ERp57-deficient cells, we found short-lived interaction of MHC class I molecules with the loading complex. Thus, in the steady state, very few MHC class I molecules were present in the loading complex. Surface H-2K(b)-peptide expression and stability were reduced, and presentation of a model antigen was decreased. Our results indicate that ERp57 does not influence the redox state of MHC class I molecules but is an essential structural component required for stable assembly of the peptide-loading complex.