Extracellular antigen processing and presentation by immature dendritic cells

In antigen presentation to CD4(+) T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving the peptide exchange factors H-2M (murine) or HLA-DM (human). In many antigen-presenting cells these processes occur in intracellular endosomal compartments, where peptides are generated and loaded onto class II MHC proteins for subsequent transport to the surface and presentation to T cells. Here, we provide evidence for an additional antigen-processing pathway in immature dendritic cells (DC). Immature DC express at the cell surface empty or peptide-receptive class II MHC molecules, as well as H-2M or HLA-DM. Secreted DC proteases act extracellularly to process intact proteins into antigenic peptides. Peptides produced by such activity are efficiently loaded onto cell surface class II MHC molecules. Together these elements comprise an unusual extracellular presentation pathway in which antigen processing and peptide loading can occur entirely outside of the cell.

在向CD4阳性T细胞（CD4(+) T cells）呈递抗原的过程中，蛋白质会被降解为肽段片段，并装载至主要组织相容性复合体II类分子（class II MHC molecules）；该过程依赖肽交换因子——小鼠H-2M与人类白细胞抗原DM（HLA-DM）介导。在多数抗原呈递细胞中，上述过程发生于胞内内体区室（intracellular endosomal compartments）：肽段在此生成并装载至MHC II类蛋白，随后被转运至细胞表面，最终呈递给T细胞。
本研究为未成熟树突状细胞（immature dendritic cells, DC）中存在的一条额外抗原加工通路提供了实验依据。未成熟DC可在细胞表面表达空载或肽可结合型MHC II类分子，同时亦可表达H-2M或HLA-DM。DC分泌的蛋白酶可在细胞外将完整蛋白质加工为抗原肽段，经该途径产生的肽段可被高效装载至细胞表面的MHC II类分子。综上，上述组分共同构成了一条非常规的细胞外抗原呈递通路，在此通路中，抗原加工与肽装载过程可完全在细胞外完成。