Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens
Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens
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DOI：
10.1073/pnas.1735556100
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发表时间：
2003-10-28
影响因子：
11.1
通讯作者：
Cresswell, P
中科院分区：
文献类型：
--
作者：
Ackerman, AL;Kyritsis, C;Cresswell, P
通常，MHC I类限制性抗原（AG）加工需要内质网（ER）内多分子肽载体复合物的作用。在这里，我们表明，来自人类树突细胞（DC）的早期吞噬体包含肽载体复合物，结合了MHC I类，132个微球蛋白，与Ag加工（TAP），钙蛋白酶，木薯蛋白，木薯粉和ERP57相关的转运蛋白，转运蛋白。抗原肽可以通过TAP转移到纯化的吞噬体中，并将其加载到同类I类分子上，从而诱导其与负载复合物的特异性解离。在DC细胞表面检测到内胚酶H敏感酶I类分子，这表明这些分子直接从吞噬体中流动。大型细胞增多症还允许内部化的可溶性AG进入含有I级加载复合物的ER样隔室。人类巨细胞的内吞作用阻断了人类巨细胞病毒蛋白US6的可溶性衍生物的阻塞，尽管将逆转录倒流到胞质溶胶中对于加工至关重要，但对于加工，I类分子与从外源AGS中衍生的肽的有效关联至关重要。这些证据共同表明，早期的吞噬体和石质体促进了DCS外源性AG的交叉表现。
Conventionally, MHC class I-restricted antigen (Ag) processing requires the action of the multimolecular peptide-loading complex within the endoplasmic reticulum (ER). Here we show that early phagosomes from human dendritic cells (DCs) contain the peptide-loading complex, incorporating MHC class I, 132 microglobulin, transporter associated with Ag processing (TAP), calreticulin, tapasin, and ERp57. Antigenic peptides could be translocated into purified phagosomes by TAP and loaded onto cognate class I molecules, inducing their specific dissociation from the loading complex. Endoglycosidase H-sensitive class I molecules were detected at the DC cell surface, suggesting that these molecules traffic there directly from phagosomes. Macropinocytosis also allowed internalized soluble Ags access to an ER-like compartment containing the class I loading complex. Blockade of TAP by endocytosis of a soluble derivative of human cytomegalovirus protein US6 confirmed that, although retrotranslocation into the cytosol is critical for processing, efficient association of class I molecules with peptides derived from exogenous Ags occurs within a compartment directly accessible to internalized proteins. Together, this evidence suggests that early phagosomes and pinosomes facilitate cross presentation of exogenous Ags by DCs.