Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages.
Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages.
复制标题
DOI：
10.1084/jem.191.7.1177
复制
发表时间：
2000-04-03
影响因子：
15.3
通讯作者：
Chapman, H A
中科院分区：
文献类型：
--
作者：
Shi, G P;Bryant, R A;Riese, R;Verhelst, S;Driessen, C;Li, Z;Bromme, D;Ploegh, H L;Chapman, H A
主要组织相容性复合物 (MHC) II 类相关不变链 (Ii) 调节 MHC II 类分子的细胞内运输和肽负载。这种负载发生在不变链内体降解为~3-kD肽（称为CLIP（II类相关不变链肽））之后。组织蛋白酶 L 和 S 分别参与胸腺和外周淋巴器官中 Ii 降解为 CLIP 的过程。然而，组织蛋白酶 S 和 L 都缺乏的小鼠的巨噬细胞可以正常加工 Ii 并将肽加载到 MHC II 类二聚体上。这两个过程都被半胱氨酸蛋白酶抑制剂阻断，表明另外的 Ii 加工酶的参与。将巨噬细胞表达的半胱氨酸蛋白酶与脾细胞和树突状细胞中发现的半胱氨酸蛋白酶进行比较，发现两种酶仅在巨噬细胞中表达：组织蛋白酶 Z 和 F。重组组织蛋白酶 Z 不会从 Ii-MHC II 类复合物中生成 CLIP，而组织蛋白酶 F 在 CLIP 生成中与组织蛋白酶 S 一样有效。巨噬细胞对组织蛋白酶 F 活性和 MHC II 类肽负载的抑制表现出相似的特异性和活性特征。这些实验表明，抗原呈递细胞 (APC) 子集中的组织蛋白酶 F 可以有效降解 Ii。因此，不同的 APC 可以使用不同的蛋白酶来介导 MHC II 类成熟和肽加载。
The major histocompatibility complex (MHC) class II–associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a ∼3-kD peptide termed CLIP (class II–associated invariant chain peptide). Cathepsins L and S have both been implicated in degradation of Ii to CLIP in thymus and peripheral lymphoid organs, respectively. However, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto MHC class II dimers normally. Both processes are blocked by a cysteine protease inhibitor, indicating the involvement of an additional Ii-processing enzyme(s). Comparison of cysteine proteases expressed by macrophages with those found in splenocytes and dendritic cells revealed two enzymes expressed exclusively in macrophages, cathepsins Z and F. Recombinant cathepsin Z did not generate CLIP from Ii–MHC class II complexes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation. Inhibition of cathepsin F activity and MHC class II peptide loading by macrophages exhibited similar specificity and activity profiles. These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading.