三肽基肽酶在MHC I类表位产生中的重要作用。

An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope.

作者信息

Seifert Ulrike, Marañón Concepción, Shmueli Ayelet, Desoutter Jean-François, Wesoloski Lisa, Janek Katharina, Henklein Peter, Diescher Susanne, Andrieu Muriel, de la Salle Henri, Weinschenk Toni, Schild Hansjörg, Laderach Diego, Galy Anne, Haas Gaby, Kloetzel Peter-M, Reiss Yuval, Hosmalin Anne

机构信息

Institut für Biochemie-Charité, Medical Faculty of the Humboldt-University Berlin, Monbijoustr. 2, 10117 Berlin, Germany.

出版信息

Nat Immunol. 2003 Apr;4(4):375-9. doi: 10.1038/ni905. Epub 2003 Feb 24.

DOI:10.1038/ni905

PMID:12598896

Abstract

Most of the peptides presented by major histocompatibility complex (MHC) class I molecules require processing by proteasomes. Tripeptidyl peptidase II (TPPII), an aminopeptidase with endoproteolytic activity, may also have a role in antigen processing. Here, we analyzed the processing and presentation of the immunodominant human immunodeficiency virus epitope HIV-Nef(73-82) in human dendritic cells. We found that inhibition of proteasome activity did not impair Nef(73-82) epitope presentation. In contrast, specific inhibition of TPPII led to a reduction of Nef(73-82) epitope presentation. We propose that TPPII can act in combination with or independent of the proteasome system and can generate epitopes that evade generation by the proteasome-system.

摘要

主要组织相容性复合体（MHC）I类分子呈递的大多数肽需要蛋白酶体进行加工。三肽基肽酶II（TPPII）是一种具有内切蛋白水解活性的氨肽酶，也可能在抗原加工中发挥作用。在此，我们分析了人树突状细胞中免疫显性的人类免疫缺陷病毒表位HIV-Nef(73-82)的加工和呈递情况。我们发现蛋白酶体活性的抑制并不损害Nef(73-82)表位的呈递。相反，TPPII的特异性抑制导致Nef(73-82)表位呈递减少。我们提出，TPPII可以与蛋白酶体系统联合作用或独立作用，并能产生逃避蛋白酶体系统产生的表位。