Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP

被引：167

作者：

Manoury, B

Mazzeo, D

Fugger, L

Viner, N

Ponsford, M

Streeter, H

Mazza, G

Wraith, DC

Watts, C ^{[1
]}

机构：

[1] Univ Dundee, Sch Life Sci, Wellcome Trust Bioctr, Div Cell Biol, Dundee DD1 5EH, Scotland

[2] Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8200 Aarhus, Denmark

[3] Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, Bristol BS8 1TD, Avon, England

来源：

NATURE IMMUNOLOGY | 2002年 / 3卷 / 02期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/ni754

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Little is known about the processing of putative human autoantigens and why tolerance is established to some T cell epitopes but not others. Here we show that a principal human HLA-DR2-restricted epitope-amino acids 85-99 of myelin basic protein, MBP(85-99)-contains a processing site for the cysteine protease asparagine endopeptidase (AEP). Presentation of this epitope by human antigen-presenting cells is inversely proportional to the amount of cellular AEP activity: inhibition of AEP in living cells greatly enhances presentation of the MBP(85-99) epitope, whereas overexpression of AEP diminishes presentation. These results indicate that central tolerance to this encephalitogenic MBP epitope may not be established because destructive processing limits its display in the thymus. Consistent with this hypothesis, AEP is expressed abundantly in thymic antigen-presenting cells.

引用

页码：169 / 174

页数：6

共 41 条

[1] High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire [J].