内质网氨基肽酶相关抗原加工（ERAAP）与主要组织相容性复合体I类分子协同作用，在内质网中对抗原肽前体进行最终切割。

Kanaseki Takayuki, Blanchard Nicolas, Hammer Gianna Elena, Gonzalez Federico, Shastri Nilabh

Division of Immunology, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.

Immunity. 2006 Nov;25(5):795-806. doi: 10.1016/j.immuni.2006.09.012.

The major histocompatibility complex class I molecules display peptides (pMHC I) on the cell surface for immune surveillance by CD8(+) T cells. These peptides are generated by proteolysis of intracellular polypeptides by the proteasome in the cytoplasm and then in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with antigen processing (ERAAP). To define the unknown mechanism of ERAAP function in vivo, we analyzed naturally processed peptides in cells with or without appropriate MHC I and ERAAP. In the absence of MHC I, ERAAP degraded the antigenic precursors in the ER. However, MHC I molecules could bind proteolytic intermediates and were essential for generation of the final peptide by ERAAP. Thus, ERAAP synergizes with MHC I to generate the final pMHC I repertoire.

主要组织相容性复合体I类分子在细胞表面展示肽段（pMHC I），以供CD8(+) T细胞进行免疫监视。这些肽段是由细胞质中的蛋白酶体对细胞内多肽进行蛋白水解产生的，然后在内质网（ER）中由与抗原加工相关的ER氨肽酶（ERAAP）进一步处理。为了确定ERAAP在体内发挥功能的未知机制，我们分析了有或没有适当的MHC I和ERAAP的细胞中天然加工的肽段。在没有MHC I的情况下，ERAAP在内质网中降解抗原前体。然而，MHC I分子可以结合蛋白水解中间体，并且对于ERAAP生成最终肽段至关重要。因此，ERAAP与MHC I协同作用以产生最终的pMHC I库。