Jiang W, Swiggard W J, Heufler C, Peng M, Mirza A, Steinman R M, Nussenzweig M C
Laboratory of Molecular Immunology, Rockefeller University, New York, New York 10021, USA.
Nature. 1995 May 11;375(6527):151-5. doi: 10.1038/375151a0.
Dendritic cells and thymic epithelial cells perform important immunoregulatory functions by presenting antigens in the form of peptides bound to cell-surface major histocompatibility complex (MHC) molecules to T cells. Whereas B cells are known to present specific antigens efficiently through their surface immunoglobins, a comparable mechanism for the capture and efficient presentation of diverse antigens by dendritic cells and thymic epithelial cells has not previously been described. We show here that their antigen-presentation function is associated with the high-level expression of DEC-205, an integral membrane protein homologous to the macrophage mannose receptor and related receptors which are able to bind carbohydrates and mediate endocytosis. DEC-205 is rapidly taken up by means of coated pits and vesicles, and is delivered to a multivesicular endosomal compartment that resembles the MHC class II-containing vesicles implicated in antigen presentation. Rabbit antibodies that bind DEC-205 are presented to reactive T-cell hybridomas 100-fold more efficiently than rabbit antibodies that do not bind DEC-205. Thus DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment.
树突状细胞和胸腺上皮细胞通过将与细胞表面主要组织相容性复合体(MHC)分子结合的肽形式的抗原呈递给T细胞,来执行重要的免疫调节功能。虽然已知B细胞通过其表面免疫球蛋白有效地呈递特定抗原,但此前尚未描述树突状细胞和胸腺上皮细胞捕获和有效呈递多种抗原的类似机制。我们在此表明,它们的抗原呈递功能与DEC-205的高水平表达相关,DEC-205是一种整合膜蛋白,与巨噬细胞甘露糖受体及相关受体同源,这些受体能够结合碳水化合物并介导内吞作用。DEC-205通过有被小窝和小泡迅速被摄取,并被递送至一种多泡内体区室,该区域类似于参与抗原呈递的含MHC II类分子的小泡。与不结合DEC-205的兔抗体相比,结合DEC-205的兔抗体被呈递给反应性T细胞杂交瘤的效率要高100倍。因此,DEC-205是一种新型的内吞受体,树突状细胞和胸腺上皮细胞可利用它将从细胞外空间捕获的抗原导向一个专门的抗原加工区室。