Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation
Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation
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DOI：
10.1073/pnas.95.8.4516
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Villadangos, JA
中科院分区：
文献类型：
--
作者：
Deussing, J;Roth, W;Villadangos, JA
通过主要组织相容性复合体（MHC）II类分子的抗原呈递需要不同蛋白酶参与内吞途径以降解内吞抗原以及MHC II类相关不变链（Ii）。到目前为止，只有半胱氨酸蛋白酶组织蛋白酶（Cat）S出现Ii的完全破坏所必需的。参与抗原自身降解的酶仍有待鉴定。体外抗原降解和使用蛋白酶抑制剂的实验表明，Cat B和Cat D（分别为两种主要的胆固醇和半胱氨酸蛋白酶）参与抗原降解。我们分析了来自Cat B或Cat D缺陷小鼠的细胞的抗原呈递特性。虽然这些蛋白酶的缺乏引起了一些抗原决定簇呈递效率的适度变化，但Cat B-/-或Cat D-/-抗原呈递细胞的总体能力不受影响。在Cat B-/-脾细胞中，Ii的降解正常进行，在Cat D-/-细胞中也是如此。我们的结论是，无论是猫B或猫D是必不可少的MHC II类介导的抗原呈递。
Antigen presentation by major histocompatibility complex (MHC) class II molecules requires the participation of different proteases in the endocytic route to degrade endocytosed antigens as well as the MHC class II-associated invariant chain (Ii). Thus far, only the cysteine protease cathepsin (Cat) S appears essential for complete destruction of Ii. The enzymes involved in degradation of the antigens themselves remain to be identified. Degradation of antigens in vitro and experiments using protease inhibitors have suggested that Cat B and Cat D, two major aspartyl and cysteine proteases, respectively, are involved in antigen degradation. We have analyzed the antigen-presenting properties of cells derived from mice deficient in either Cat B or Cat D. Although the absence of these proteases provoked a modest shift in the efficiency of presentation of some antigenic determinants, the overall capacity of Cat B-/- or Cat D-/- antigen-presenting cells was unaffected. Degradation of Ii proceeded normally in Cat B-/- splenocytes, as it did in Cat D-/- cells. We conclude that neither Cat B nor Cat D are essential for MHC class II-mediated antigen presentation.