Extracellular antigen processing and presentation by immature dendritic cells

Extracellular antigen processing and presentation by immature dendritic cells
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DOI:
10.1073/pnas.96.26.15056
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发表时间:
1999-12-21
影响因子:
11.1
通讯作者:
Stern, LJ
Stern, LJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Santambrogio, L;Sato, AK;Stern, LJ

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在抗原呈递给 CD4(+) T 细胞的过程中,蛋白质被降解为肽片段,并在涉及肽交换因子 H-2M(鼠)或 HLA-DM(人)的过程中加载到 II 类 MHC 分子上。在许多抗原呈递细胞中,这些过程发生在细胞内体区室中,其中生成肽并加载到 II 类 MHC 蛋白上,随后转运到表面并呈递给 T 细胞。在这里,我们为未成熟树突状细胞 (DC) 中的额外抗原加工途径提供了证据,未成熟树突状细胞在细胞表面表达空或肽受体 II 类 MHC 分子,以及 H-2M 或 HLA-DM。分泌的 DC 蛋白酶在细胞外发挥作用,将完整蛋白质加工成抗原肽。这种活性产生的肽被有效地装载到细胞表面 II 类 MHC 分子上,这些元件一起构成了一种不寻常的细胞外呈递途径,其中抗原加工和肽装载可以完全在细胞外发生。
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.