T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells
T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells
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DOI：
10.1053/j.gastro.2007.02.043
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发表时间：
2007-05-01
期刊：
影响因子：
29.4
通讯作者：
Heyman, Martine
中科院分区：
文献类型：
--
作者：
Mallegol, Julia;Van Niel, Guillaume;Heyman, Martine
背景与目的：肠上皮细胞释放携带主要组织相容性复合体II类/多肽复合体的抗原提呈囊泡(外体)，刺激体内特异性免疫反应。为了进一步研究人上皮外切体在抗原提呈中的作用，我们在体外分析了它们负载抗原肽、结合免疫靶细胞和诱导T细胞活化的能力。方法：在人单核细胞来源的树突状细胞(DC)存在或不存在的情况下，检测表达HLADR4的肠上皮细胞株T84的外体负载HLADR4特异性多肽H-3-HSA-76的能力和激活HLADR4限制性T细胞杂交瘤的能力。用流式细胞仪和共聚焦显微镜分析异硫氰酸酯标记的外切体与T细胞和DC的相互作用。结果：T84来源的外切体富含CD9、CD81、CD82和A33抗原，能够与人血清白蛋白-76肽特异性结合在HLADR4分子上，并优先与DC相互作用。载人血清白蛋白的外切体不能直接激活T细胞杂交瘤，但可通过树突状细胞诱导T细胞的高效激活。当HSA多肽与胞外体的HLA-DR4分子结合而不是以可溶性形式结合时，DC提呈多肽的阈值显著降低(x 10(-3))。结论：肠上皮细胞释放的外源多肽与主要组织相容性复合体11分子结合，并优先与DC相互作用，增强T细胞的多肽呈递功能。上皮外切体通过介导微量的管腔抗原信息的传递和促进粘膜表面的免疫监视，在管腔抗原和局部免疫细胞之间建立了强大的联系。
Background & Aims: Intestinal epithelial cells release antigen-presenting vesicles (exosomes) bearing major histocompatibility complex class II/peptide complexes stimulating specific immune responses in vivo. To characterize further the role of human epithelial exosomes in antigen presentation, their capacity to load antigenic peptides, bind immune target cells, and induce T-cell activation was analyzed in vitro. Methods: The capacity of exosomes derived from the HLA-DR4-expressing, intestinal epithelial cell line T84 to load the HLA-DR4-specific peptide H-3-HSA 64-76 and to activate a HLA-DR4-restricted T-cell hybridoma was tested in the presence or absence of human monocyte-derived dendritic cells (DCs). Interaction of fluorescein isothiocyanate-labeled exosomes with T cells and DCs was analyzed by flow cytometry and confocal microscopy. Results: T84-derived exosomes, enriched in CD9, CD81, CD82, and A33 antigen, were capable of binding specifically human serum albumin (HSA) 64-76 peptide on HLA-DR4 molecules and of interacting preferentially with DCs. HSA-loaded exosomes were unable to activate the T-cell hybridoma directly but induced a productive T-cell activation through DCs. When HSA peptide was bound to exosomal HLA-DR4 molecules instead of in a soluble form, the threshold of peptide presentation by DCs was markedly decreased (x 10(-3)). Conclusions: Exosomes released by intestinal epithelial cells bear exogenous peptides complexed to major histocompatibility complex class 11 molecules and interact preferentially with DCs, strongly potentiating peptide presentation to T cells. Epithelial exosomes constitute a powerful link between luminal antigens and local immune cells by mediating the transfer of tiny amounts of luminal antigenic information and facilitating immune surveillance at mucosal surfaces.