Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos J A, Ploegh H, Peters C, Rudensky A Y
Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Science. 1998 Apr 17;280(5362):450-3. doi: 10.1126/science.280.5362.450.
Degradation of invariant chain (Ii) is a critical step in major histocompatibility complex class II-restricted antigen presentation. Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)-derived antigen-presenting cells (APCs). Consequently, positive selection of CD4+ T cells was reduced. Because different cysteine proteinases are responsible for specific Ii degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative selection may be distinct. The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4+ T cell responsiveness in vivo.
恒定链（Ii）的降解是主要组织相容性复合体II类限制抗原呈递中的关键步骤。组织蛋白酶L被发现是皮质胸腺上皮细胞（cTECs）中Ii降解所必需的，但在骨髓（BM）来源的抗原呈递细胞（APCs）中并非如此。因此，CD4+ T细胞的阳性选择减少。由于不同的半胱氨酸蛋白酶负责cTECs和BM来源的APCs中Ii的特定降解步骤，介导阳性和阴性选择的细胞中的蛋白水解环境可能不同。以组织特异性方式参与II类呈递的蛋白酶的鉴定提示了一种在体内操纵CD4+ T细胞反应性的潜在方法。
