MHC class I antigen processing regulated by cytosolic proteolysis - short cuts that alter peptide generation

被引:32
作者
Kessler, BM
Glas, R
Ploegh, HL
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] MTC, Karolinska Inst, S-17177 Stockholm, Sweden
关键词
cytosolic proteolysis; proteasome inhibitor; MNC class I antigens; cytotoxic T lymphocytes; tumor-associated antigens; oligopeptidases;
D O I
10.1016/S0161-5890(02)00100-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytotoxic T lymphocyte (CTL)-mediated immune responses rely on the efficiency of MHC class I ligand generation and presentation by antigen presenting cells (APCs). Whereas the abnormal expression of MHC molecules and transporters associated with antigen processing (TAPs) are commonly discussed as factors that modulate antigen presentation, much less is known about possible regulatory mechanisms at the level of proteolysis responsible for the generation of antigenic peptides. The ubiquitin-proteasome system is recognized as the major component responsible for this process in the cytosol and its activity can be regulated by cytokines, such as IFN-gamma. However, new evidence suggests the involvement of other proteases that can contribute to cytosolic proteolysis and therefore, to the quality and quantity of antigen production. Here, we review recent findings on an increasing number of proteolytic enzymes linked to antigen presentation, and we discuss how regulation of cytosolic protease activities might have implications for immune escape mechanisms that could be used by tumor cells and pathogens. (C) 2002 Published by Elsevier Science Ltd.
引用
收藏
页码:171 / 179
页数:9
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