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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Langerhans cells cross-present antigen derived from skin
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Langerhans cells cross-present antigen derived from skin

机译：郎格罕斯细胞交叉呈递来自皮肤的抗原

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摘要

Dendritic cells (DC) efficiently cross-present exogenous antigen on MHC class I molecules to CD8(+) T cells. However, little is known about cross-presentation by Langerhans cells (LC), the DCs of the epidermis. Therefore, we investigated this issue in detail. Isolated murine LCs were able to cross-present soluble ovalbumin protein on MHC-class I molecules to antigen-specific CD8(+) T cells, albeit less potently than the CD8(+) DC subsets from spleen. Furthermore, LCs cross-presented cell-associated ovalbumin peptide and protein expressed by neighboring keratinocytes. Use of transporter associated with antigen processing (TAP-1)-deficient mice suggested a TAP-dependent pathway. Similar observations were made with migratory LC. Antigen expressed in the epidermis was ingested by LCs during migration from the epidermis and presented to antigen-specific T cells in vitro. Cross-presentation of ovalbumin protein by LCs induced IFN-gamma production and cytotoxicity in antigen-specific CD8(+) T cells. Additionally, epicutaneous application of ovalbumin protein induced in vivo proliferation of OT-I T cells in the draining lymph nodes; this was markedly enhanced when antigen was applied to inflamed, barrier-disrupted skin. Thus, LCs cross-present exogenous antigen to CD8(+) T cells and induce effector functions, like cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.
机译：树突状细胞（DC）有效地将MHC I类分子上的外源抗原交叉呈递给CD8（+）T细胞。然而，人们对朗格​​汉斯细胞（LC）（表皮的DC）的交叉呈递知之甚少。因此，我们详细研究了此问题。分离的鼠类LC能够将MHC I类分子上的可溶性卵清蛋白蛋白质交叉呈递给抗原特异性CD8（+）T细胞，尽管其效力不及脾脏的CD8（+）DC子集。此外，LCs交叉呈递与细胞相关的卵清蛋白肽和邻近角质形成细胞表达的蛋白质。与抗原加工（TAP-1）缺陷小鼠相关的转运蛋白的使用提示了TAP依赖性途径。用迁徙LC也得到了类似的观察结果。在表皮中表达的抗原在从表皮迁移的过程中被LC摄取，并在体外呈递给抗原特异性T细胞。 LC交叉呈递卵清蛋白蛋白诱导抗原特异性CD8（+）T细胞中的IFN-γ产生和细胞毒性。另外，卵清蛋白蛋白的表皮应用诱导了引流淋巴结中的OT-1 T细胞的体内增殖。当抗原应用于发炎，屏障破坏的皮肤时，这种作用显着增强。因此，LC将外源抗原交叉呈递给CD8（+）T细胞，并诱导效应子功能，如细胞因子的产生和细胞毒性，从而可能在表皮疫苗接种方法中发挥关键作用。

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