Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells
Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells
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DOI：
10.1038/ni1147
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发表时间：
2005-01-01
影响因子：
30.5
通讯作者：
Cresswell, P
中科院分区：
文献类型：
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作者：
Ackerman, AL;Kyritsis, C;Cresswell, P
在树突状细胞（DCs）中，来自内化颗粒底物的肽段可被主要组织相容性复合体（MHC）I类分子有效地交叉呈递。外源性可溶性抗原也可被DCs呈递，但效率明显较低。在此我们表明，颗粒性抗原和可溶性抗原使用不同的转运途径。已表明颗粒性抗原可进入具有交叉呈递能力的外周内质网（ER）样吞噬体，而我们在此表明，逃避蛋白水解的可溶性蛋白进入内质网腔。从那里，它们可能通过内质网相关降解所建立的途径转运到细胞质中，并且其衍生的肽段可能被转运回内质网以与MHC I类分子结合。涉及DCs将可溶性蛋白组成性逆向转运到内质网的MHC I类呈递可能促进DC对其细胞外环境成分的耐受性。
In dendritic cells (DCs), peptides derived from internalized particulate substrates are efficiently cross-presented by major histocompatibility complex (MHC) class I molecules. Exogenous soluble antigens are also presented by DCs but with substantially lower efficiency. Here we show that particulate and soluble antigens use different transport pathways. Particulate antigens have been shown to access peripheral endoplasmic reticulum (ER)-like phagosomes that are competent for cross-presentation, whereas we show here that soluble proteins that escape proteolysis enter the lumen of the ER. From there, they may be translocated into the cytosol by the pathway established for ER-associated degradation and their derived peptides may be transported back into the ER for binding by MHC class I molecules. MHC class I presentation involving the constitutive retrograde transport of soluble proteins to the ER by DCs may facilitate DC tolerance to components of their extracellular environment.