York Ian A, Chang Shih-Chung, Saric Tomo, Keys Jennifer A, Favreau Janice M, Goldberg Alfred L, Rock Kenneth L
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
Nat Immunol. 2002 Dec;3(12):1177-84. doi: 10.1038/ni860. Epub 2002 Nov 18.
Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an eight-residue ovalbumin epitope from precursors extended on the NH2 terminus that were generated either in the ER or cytosol. Purified ERAP1 also trimmed nearly half the nine-residue peptides tested. By destroying such nine-residue peptides in normal human cells, ERAP1 reduced the overall supply of antigenic peptides. However, after interferon-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation.
内质网氨基肽酶1（ERAP1）似乎专门用于产生呈递在I类主要组织相容性复合体分子上的肽段。我们发现，纯化的ERAP1会修剪十个或更长残基的肽段，但不会修剪八个残基的肽段。在体内，ERAP1可增强从在内质网或细胞质中产生的NH2末端延伸的前体中产生八残基卵清蛋白表位。纯化的ERAP1还修剪了近一半测试的九残基肽段。通过在正常人类细胞中破坏此类九残基肽段，ERAP1减少了抗原肽的总体供应。然而，在干扰素-γ处理后，这会导致蛋白酶体产生更多NH2末端延伸的抗原前体，ERAP1增加了用于MHC I类抗原呈递的肽段供应。
