Control of cross-presentation during dendritic cell maturation
Control of cross-presentation during dendritic cell maturation
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DOI：
10.1002/eji.200324508
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发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Amigorena, S
中科院分区：
文献类型：
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作者：
Gil-Torregrosa, BC;Lennon-Duménil, AM;Amigorena, S
大多数细胞毒性免疫反应的启动需要 MHC I 类限制性内化抗原呈递给 CD8(+) T 淋巴细胞，这一过程称为交叉呈递。树突状细胞 (DC) 是唯一激活初始 T 细胞的抗原呈递细胞，在调理抗原或免疫复合物内化后，交叉呈递特别有效，这些抗原或免疫复合物通过与抗原加工 (TAP) 依赖性 MHC I 类抗原呈递途径相关的蛋白酶体和转运蛋白交叉呈递。我们现在表明 FcgammaR 介导的交叉呈递在 DC 成熟过程中受到严格调节。交叉呈递在脂多糖激活后很快就会增加，然后在完全成熟的细胞中受到抑制。交叉呈递的最初诱导是由于抗原内化和向细胞质的递送的增加以及蛋白酶体和 TAP 活性的轻微增加所致。随后成熟 DC 中交叉呈递的阻断是抗原内化和胞质递送选择性下调的结果，而蛋白酶体和 TAP 活性继续上升。因此，FcgammaR 介导的交叉呈递在 DC 成熟过程中通过选择性控制抗原内化和转运至胞质溶胶来调节。
The initiation of most cytotoxic immune responses requires MHC class I-restricted presentation of internalized antigens to CD8(+) T lymphocytes, a process called cross-presentation. In dendritic cells (DC), the only antigen-presenting cells that activate naive T cells, cross-presentation is particularly efficient after internalization of opsonized antigens or immune complexes, which are cross-presented through a proteasome- and transporter associated with antigen processing (TAP)-dependent MHC class I antigen presentation pathway. We now show that FcgammaR-mediated cross-presentation is tightly regulated during DC maturation. Cross-presentation increases soon after activation by lipopolysaccharides, and it is then inhibited in fully mature cells. The initial induction of cross-presentation results from an increase of both antigen internalization and delivery to the cytosol, and from a slight rise in the activity of the proteasome and TAP. The subsequent block of cross-presentation in mature DC is a consequence of the selective down-modulation of antigen internalization and cytosolic delivery, while proteasome and TAP activities continue to rise. Therefore, FcgammaR-mediated cross-presentation is regulated during DC maturation by the selective control of antigen internalization and transport to the cytosol.