Mizuochi T, Yee S T, Kasai M, Kakiuchi T, Muno D, Kominami E
Department of Bacterial and Blood Products, National Institute of Health, Tokyo, Japan.
Immunol Lett. 1994 Dec;43(3):189-93. doi: 10.1016/0165-2478(94)90221-6.
The effect of highly selective inhibitors of cathepsins on the processing of ovalbumin (OVA) and the presentation of an OVA-derived antigenic peptide (OVA323-339) by antigen presenting cells (APC) was investigated. Both CA-074 (a specific inhibitor of cathepsin B) and pepstatin A (a specific inhibitor of cathepsin D) showed an inhibitory effect on the IL-2 production from an OVA-specific, I-Ad-restricted helper T (Th) cell clone upon stimulation with OVA presented by the I-Ad-positive APC. In contrast, the presentation of the antigenic epitope, OVA323-339, to the same Th clone was not inhibited by either CA-074 or pepstatin A alone, nor even by the mixture of both inhibitors. When APC were treated with cathepsin inhibitor for 24 h, and then antigen and Th were added to the culture, the presentation of not only OVA but also an OVA-derived antigenic peptide was inhibited by either cathepsin inhibitor alone. In addition, the expression of invariant chain on APC was significantly augmented by the pretreatment of APC with either cathepsin inhibitor. Two main conclusions are drawn from these results. First, not only aspartyl protease, such as cathepsin D, but also thiol protease, such as cathepsin B, is involved in antigen processing by APC. Second, both cathepsin B and cathepsin D are necessary for degradation of the invariant chain (Ii) from the MHC class II alpha beta heterodimer in endosomes in order to express functional MHC class II molecules for binding antigenic peptides.
研究了组织蛋白酶的高选择性抑制剂对卵清蛋白（OVA）加工以及抗原呈递细胞（APC）呈递OVA衍生抗原肽（OVA323 - 339）的影响。组织蛋白酶B的特异性抑制剂CA - 074和组织蛋白酶D的特异性抑制剂胃蛋白酶抑素A，在由I - Ad阳性APC呈递OVA刺激时，均对OVA特异性、I - Ad限制的辅助性T（Th）细胞克隆的IL - 2产生表现出抑制作用。相比之下，单独的CA - 074或胃蛋白酶抑素A，甚至这两种抑制剂的混合物，均未抑制相同Th克隆对抗原表位OVA323 - 339的呈递。当APC用组织蛋白酶抑制剂处理24小时，然后向培养物中加入抗原和Th时，单独的任何一种组织蛋白酶抑制剂均抑制了OVA以及OVA衍生抗原肽的呈递。此外，用任何一种组织蛋白酶抑制剂预处理APC后，APC上恒定链的表达均显著增加。从这些结果得出两个主要结论。第一，不仅天冬氨酸蛋白酶如组织蛋白酶D，而且巯基蛋白酶如组织蛋白酶B，都参与APC的抗原加工。第二，组织蛋白酶B和组织蛋白酶D对于在内体中从MHC II类αβ异二聚体降解恒定链（Ii）都是必需的，以便表达用于结合抗原肽的功能性MHC II类分子。
