组织蛋白酶S对CD1功能以及NK1.1(+) T细胞选择与成熟的调控
Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S.
作者信息
Riese R J, Shi G P, Villadangos J, Stetson D, Driessen C, Lennon-Dumenil A M, Chu C L, Naumov Y, Behar S M, Ploegh H, Locksley R, Chapman H A
机构信息
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Immunity. 2001 Dec;15(6):909-19. doi: 10.1016/s1074-7613(01)00247-3.
NK1.1(+) T cells develop and function through interactions with cell surface CD1 complexes. In I-A(b) mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of the CD1-restricted antigen, alpha-galactosylceramide (alpha-GalCer). CD1 dysfunction is secondary to defective trafficking of CD1, which colocalizes with Ii fragments and accumulates within endocytic compartments of cathepsin S(-/-) DCs. I-A(k), cathepsin S(-/-) mice do not accumulate class II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is critically linked to processing of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.
NK1.1(+) T细胞通过与细胞表面CD1复合物相互作用而发育并发挥功能。在缺乏恒定链（Ii）加工酶组织蛋白酶S的I-A(b)小鼠中，NK1.1(+) T细胞的选择和功能受损。在体外，来自组织蛋白酶S(-/-)小鼠的胸腺树突状细胞（DCs）表现出CD1限制性抗原α-半乳糖神经酰胺（α-GalCer）递呈缺陷。CD1功能障碍继发于CD1的转运缺陷，CD1与Ii片段共定位并在组织蛋白酶S(-/-) DCs的内吞小室中积累。I-A(k)组织蛋白酶S(-/-)小鼠不会积累II类相关Ii片段，因此不会表现出CD1异常。因此，CD1的功能与Ii的加工密切相关，揭示了MHC II类单倍型和组织蛋白酶S活性作为NK T细胞的调节因子。
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