In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides
In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides
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DOI：
10.1038/ni1409
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发表时间：
2007-01-01
影响因子：
30.5
通讯作者：
Shastri, Nilabh
中科院分区：
文献类型：
--
作者：
Hammer, Gianna Elena;Gonzalez, Federico;Shastri, Nilabh
细胞毒性T细胞的免疫监视需要细胞产生多种多样的肽谱，以供主要组织相容性复合体（MHC）I类分子呈递。这些肽是由蛋白水解产生的，蛋白水解开始于细胞质，并通过独特的氨肽酶ERAAP在内质网中继续。ERAAP修饰肽库的总体程度和ERAAP缺陷的免疫学后果尚不清楚。在这里，我们表明ERAAP缺陷小鼠的肽-MHC库缺少许多肽。此外，ERAAP缺陷的细胞呈现许多不稳定的和结构独特的肽-MHC复合物，其引起有效的CD 8（+）T细胞和B细胞应答。因此，ERAAP是肽-MHC库的“典型编辑器”，矛盾的是，它的缺失增强了免疫原性。
Immunosurveillance by cytotoxic T cells requires that cells generate a diverse spectrum of peptides for presentation by major histocompatibility complex ( MHC) class I molecules. Those peptides are generated by proteolysis, which begins in the cytoplasm and continues in the endoplasmic reticulum by the unique aminopeptidase ERAAP. The overall extent to which trimming by ERAAP modifies the peptide pool and the immunological consequences of ERAAP deficiency are unknown. Here we show that the peptide-MHC repertoire of ERAAP-deficient mice was missing many peptides. Furthermore, ERAAP-deficient cells presented many unstable and structurally unique peptide-MHC complexes, which elicited potent CD8(+) T cell and B cell responses. Thus, ERAAP is a 'quintessential editor' of the peptide-MHC repertoire and, paradoxically, its absence enhances immunogenicity.