Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A
Basel Institute for Immunology, Switzerland.
Nature. 1997 Aug 21;388(6644):782-7. doi: 10.1038/42030.
Dendritic cells have the remarkable property of presenting any incoming antigen. To do so they must not only capture antigens with high efficiency and broad specificity, but must also maximize their capacity to load class II molecules of the major histocompatibility complex (MHC) with antigenic peptides in order to present a large array of epitopes from different proteins, each at a sufficient copy number. Here we show that formation of peptide-MHC class II complexes is boosted by inflammatory stimuli that induce maturation of dendritic cells. In immature dendritic cells, class II molecules are rapidly internalized and recycled, turning over with a half-life of about 10 hours. Inflammatory stimuli induce a rapid and transient boost of class II synthesis, while the half-life of class II molecules increases to over 100 hours. These coordinated changes result in the rapid accumulation of a large number of long-lived peptide-loaded MHC class II molecules capable of stimulating T cells even after several days. The capacity of dendritic cells to load many antigenic peptides over a short period of initial exposure to inflammatory stimuli could favour presentation of infectious antigens.
树突状细胞具有呈递任何进入的抗原的显著特性。为此,它们不仅必须高效且广泛特异性地捕获抗原,还必须最大限度地提高其用抗原肽加载主要组织相容性复合体(MHC)II类分子的能力,以便呈递来自不同蛋白质的大量表位,每个表位都有足够的拷贝数。在这里,我们表明,诱导树突状细胞成熟的炎性刺激会促进肽-MHC II类复合物的形成。在未成熟的树突状细胞中,II类分子会迅速内化并循环利用,半衰期约为10小时。炎性刺激会诱导II类分子合成迅速且短暂地增加,而II类分子的半衰期会增加到超过100小时。这些协调的变化导致大量长寿命的负载肽的MHC II类分子迅速积累,即使在数天后也能够刺激T细胞。树突状细胞在最初接触炎性刺激的短时间内加载许多抗原肽的能力可能有利于呈递感染性抗原。