T84-Intestinal Epithelial Exosomes Bear MHC Class II/Peptide Complexes Potentiating Antigen Presentation by Dendritic Cells

微泡 抗原处理 抗原呈递 MHC I级 抗原提呈细胞 主要组织相容性复合体 交叉展示 抗原 化学 树突状细胞 细胞毒性T细胞 免疫学 外体 细胞生物学 分子生物学 体外 生物 免疫系统 T细胞 生物化学 基因 小RNA
作者
Julia Mallegol,Guillaume van Niel,Corinne Lebreton,Yves Lepelletier,Céline Candalh,Christophe Dugave,Joan K. Heath,Graça Raposo,Nadine Cerf‐Bensussan,Martine Heyman
出处
期刊:Gastroenterology [Elsevier]
卷期号:132 (5): 1866-1876 被引量:242
标识
DOI:10.1053/j.gastro.2007.02.043
摘要

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.The capacity of exosomes derived from the HLA-DR4-expressing, intestinal epithelial cell line T84 to load the HLA-DR4-specific peptide (3)H-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.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 (x10(-3)).Exosomes released by intestinal epithelial cells bear exogenous peptides complexed to major histocompatibility complex class II 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.
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