The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules
The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules
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DOI：
10.1038/ni1286
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发表时间：
2006-01-01
影响因子：
30.5
通讯作者：
Shastri, N
中科院分区：
文献类型：
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作者：
Hammer, GE;Gonzalez, F;Shastri, N
主要组织相容性复合体（MHC）I类分子呈递数千种肽，以允许CD 8（+）T细胞检测异常的细胞内蛋白。用于产生肽的抗原加工途径始于细胞质，并且MHC分子装载在内质网中。然而，内质网中肽库的性质和在该隔室中发生的蛋白水解事件尚不清楚。我们通过产生缺乏与抗原加工相关的内质网氨肽酶（ERAAP）的小鼠来解决这些问题。我们发现ERAAP的缺失破坏了内质网中天然加工肽的产生，降低了肽-MHC I类复合物的稳定性，并减少了CD 8（+）T细胞的反应。因此，内质网中ERAAP对抗原肽的修饰对于产生正常的加工肽库是必不可少的。
Major histocompatibility complex (MHC) class I molecules present thousands of peptides to allow CD8(+) T cells to detect abnormal intracellular proteins. The antigen-processing pathway for generating peptides begins in the cytoplasm, and the MHC molecules are loaded in the endoplasmic reticulum. However, the nature of peptide pool in the endoplasmic reticulum and the proteolytic events that occur in this compartment are unclear. We addressed these issues by generating mice lacking the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). We found that loss of ERAAP disrupted the generation of naturally processed peptides in the endoplasmic reticulum, decreased the stability of peptide-MHC class I complexes and diminished CD8(+) T cell responses. Thus, trimming of antigenic peptides by ERAAP in the endoplasmic reticulum is essential for the generation of the normal repertoire of processed peptides.