Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells
Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells
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DOI：
10.1182/blood-2003-06-1801
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发表时间：
2003-12-15
期刊：
影响因子：
20.3
通讯作者：
Larsson, M
中科院分区：
文献类型：
--
作者：
Fonteneau, JF;Kavanagh, DG;Larsson, M
外源性抗原的主要组织相容性复合体（MHC）I类呈递是使专职抗原呈递细胞（APC）能够诱导针对不能进入经典MHC I类途径的病毒和肿瘤的CD8（+）T细胞应答的机制。我们的特点是摄取，加工，和MHC I类交叉呈递人树突状细胞（DC）的细胞相关抗原来自生理相关的来源，即，牛痘病毒感染的凋亡和坏死细胞。我们表明，交叉呈递是一个快速的过程，在死亡细胞摄取后2至4小时内可检测到，并且在酸性内体隔室中通过组织蛋白酶D的蛋白水解对于交叉呈递是必不可少的。当细胞的吞噬或巨噬细胞功能被抑制时，呈递被取消，并且依赖于与抗原加工相关的转运蛋白，对布雷菲德菌素A敏感，并且需要功能性蛋白酶体。总之，这些数据表明，来自凋亡和坏死细胞的抗原需要进入胞质溶胶与传统的MHC I类途径相交，用于呈递胞质溶胶蛋白。
Major histocompatibility complex (MHC) class I presentation of exogenous antigens is the mechanism enabling professional antigen-presenting cells (APCs) to induce CD8(+) T-cell responses against viruses and tumors that do not have access to the classical MHC class I pathway. We have characterized the uptake, processing, and MHC class I cross-presentation by human dendritic cells (DCs) of cell-associated antigens derived from physiologically relevant sources, namely, vaccinia virus-infected apoptotic and necrotic cells. We show that cross-presentation is a rapid process, detectable within 2 to 4 hours after uptake of dead cells, and that proteolysis by cathepsin D in an acidic endosomal compartment is essential for cross-presentation. The presentation is abolished when the phagocytic or macropinocytic functions of the cells are inhibited and is dependent on transporter associated with antigen processing, sensitive to brefeldin A, and requires functional proteasomes. Altogether, these data suggest that antigens derived from apoptotic and necrotic cells require access to the cytosol to intersect with the conventional MHC class I pathway for presentation of cytosolic proteins.