Kessler Benedikt M, Glas Rickard, Ploegh Hidde L
Department of Pathology, Harvard Medical School, Room 137, Building D2, 200 Longwood Avenue, Boston, MA 02115, USA.
Mol Immunol. 2002 Oct;39(3-4):171-9. doi: 10.1016/s0161-5890(02)00100-1.
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.
细胞毒性T淋巴细胞（CTL）介导的免疫反应依赖于抗原呈递细胞（APC）产生和呈递MHC I类配体的效率。虽然MHC分子和与抗原加工相关的转运体（TAP）的异常表达通常被认为是调节抗原呈递的因素，但对于负责抗原肽产生的蛋白水解水平上可能的调节机制却知之甚少。泛素-蛋白酶体系统被认为是胞质溶胶中负责这一过程的主要成分，其活性可受细胞因子如IFN-γ的调节。然而，新证据表明其他蛋白酶也参与其中，这些蛋白酶可促进胞质蛋白水解，进而影响抗原产生的质量和数量。在此，我们综述了与抗原呈递相关的越来越多的蛋白水解酶的最新研究发现，并讨论了胞质蛋白酶活性的调节如何可能影响肿瘤细胞和病原体可能采用的免疫逃逸机制。
