浆细胞样树突状细胞在主要组织相容性复合体I类分子上对病毒抗原进行不依赖蛋白酶体的直接交叉呈递。

Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I.

作者信息

Di Pucchio Tiziana, Chatterjee Bithi, Smed-Sörensen Anna, Clayton Sandra, Palazzo Adam, Montes Monica, Xue Yaming, Mellman Ira, Banchereau Jacques, Connolly John E

机构信息

Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, Texas 75204, USA.

出版信息

Nat Immunol. 2008 May;9(5):551-7. doi: 10.1038/ni.1602. Epub 2008 Mar 30.

Abstract

Although plasmacytoid dendritic cells (pDCs) respond to virus replication in a nonspecific way by producing large amounts of type I interferon, a rapid, direct function for pDCs in activating antiviral lymphocytes is less apparent. Here we show that pDCs were able to rapidly initiate antigen-specific antiviral CD8+ T cell responses. After being exposed to virus, pDCs efficiently and rapidly internalized exogenous viral antigens and then presented those antigens on major histocompatibility complex (MHC) class I to CD8+ T cells. Processing of exogenous antigen occurred in endocytic organelles and did not require transit of antigen to the cytosol. Intracellular stores of MHC class I partially localized together with the transferrin receptor and internalized transferrin in endosomes, which suggested that such recycling endosomes are sites for loading peptide onto MHC class I or for peptide transit. Our data demonstrate that pDCs use 'ready-made' stores of MHC class I to rapidly present exogenous antigen to CD8+ T cells.

摘要

虽然浆细胞样树突状细胞(pDC)通过产生大量I型干扰素以非特异性方式对病毒复制作出反应,但pDC在激活抗病毒淋巴细胞方面的快速、直接功能尚不明显。在此我们表明,pDC能够快速启动抗原特异性抗病毒CD8+ T细胞反应。暴露于病毒后,pDC高效且迅速地内化外源性病毒抗原,然后将这些抗原呈递至主要组织相容性复合体(MHC)I类分子上,呈递给CD8+ T细胞。外源性抗原的加工发生在内吞细胞器中,且不需要抗原转运至胞质溶胶。MHC I类分子的细胞内储存部分与转铁蛋白受体共定位,并在内体中内化转铁蛋白,这表明此类循环内体是将肽加载到MHC I类分子上或进行肽转运的位点。我们的数据表明,pDC利用MHC I类分子的“现成”储存库快速将外源性抗原呈递给CD8+ T细胞。

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