Presentation of peptide antigens by mouse CD1 requires endosomal localization and protein antigen processing.

Presentation of peptide antigens by mouse CD1 requires endosomal localization and protein antigen processing.
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小鼠 CD1 呈递肽抗原需要内体定位和蛋白质抗原加工。

DOI:
10.1073/pnas.95.24.14314
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发表时间:
1998
影响因子:
11.1
通讯作者:
Kronenberg,M
Kronenberg,M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tangri,S;Brossay,L;Burdin,N;Lee,DJ;Corr,M;Kronenberg,M

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据报道,小鼠 CD1(mCD1) 分子可呈递两种类型的抗原:肽或蛋白质和糖脂 α-半乳糖神经酰胺。在这里,我们证明蛋白质抗原鸡卵清蛋白 (Ova) 必须经过加工才能产生由 mCD1 呈递给 CD8+T 细胞的肽。鸡卵子的加工和 mCD1 介导的呈递取决于内体定位,因为内体酸化和内体回收途径的抑制剂会阻断 T 细胞反应性。此外,mCD1 的细胞质尾部突变体会破坏内体定位,从而大大降低了向 mCD1 限制性细胞呈递 Ova 的能力。然而,新合成的 mCD1 分子并不是 Ova 呈递所必需的,这表明需要从细胞表面回收分子。由于这些数据表明 mCD1 转运至内体,在那里它可以结合源自外源蛋白的肽,因此我们得出结论,mCD1 的肽抗原呈递可能是一种自然发生的现象。在竞争测定中,α-半乳糖神经酰胺不会抑制 Ova 呈递,并且糖脂的呈递不会被过量的 Ova 或源自其的肽表位所抑制。这表明,尽管脂质和肽呈递都可能自然发生,但 mCD1 与这两种类型的抗原的相互作用可能不同。
Mouse CD1(mCD1) molecules have been reported to present two types of antigens: peptides or proteins and the glycolipid α-galactosylceramide. Here, we demonstrate that a protein antigen, chicken ovalbumin (Ova), must be processed to generate peptides presented by mCD1 to CD8+T cells. The processing and mCD1-mediated presentation of chicken Ova depend on endosomal localization because inhibitors of endosomal acidification and endosomal recycling pathways block T cell reactivity. Furthermore, a cytoplasmic tail mutant of mCD1, which disrupts endosomal localization, has a greatly reduced capacity to present Ova to mCD1 restricted cells. Newly synthesized mCD1 molecules, however, are not required for Ova presentation, suggesting that molecules recycling from the cell surface are needed. Because of these data showing that mCD1 trafficks to endosomes, where it can bind peptides derived from exogenous proteins, we conclude that peptide antigen presentation by mCD1 is likely to be a naturally occurring phenomenon. In competition assays, α-galactosylceramide did not inhibit Ova presentation, and presentation of the glycolipid was not inhibited by excess Ova or the peptide epitope derived from it. This suggests that, although both lipid and peptide presentation may occur naturally, mCD1 may interact differently with these two types of antigens.
DOI: 10.1038/360593a0
发表时间: 1992-12-10
期刊: NATURE
影响因子: 64.8
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DOI: 10.4049/jimmunol.161.7.3271
发表时间: 1998-10
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DOI: 10.1126/science.7542403
发表时间: 1995-07-14
期刊: SCIENCE
影响因子: 56.9
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DOI: 10.1016/s1074-7613(00)80425-2
发表时间: 1997-02-01
期刊: IMMUNITY
影响因子: 32.4
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通讯作者: Kronenberg, M