Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I.

作者: Sophie K. Horrevorts , Sanne Duinkerken , Karien Bloem , Pablo Secades , Hakan Kalay

DOI: 10.3389/FIMMU.2018.01231

关键词: Cross-presentationT cellMHC class ICell biologyChemistryToll-like receptorDC-SIGNCD8InternalizationAntigen

摘要: DC-SIGN is an antigen uptake receptor expressed on dendritic cells (DCs) with specificity for glycans present a broad variety of pathogens and capable directing its cargo to MHC-I MHC-II pathways the induction CD8+ CD4+ T cell responses, respectively. Therefore, very promising target delivery anti-cancer vaccination. Although endocytic route leading presentation characterized large extent, mechanisms controlling targeted cross-presentation exogenous peptides MHC-I, are not completely resolved yet. In this paper, we used imaging flow cytometry antigen-specific investigate intracellular fate in human DCs. Our data demonstrates that immature DCs toll-like 4 (TLR4) stimulated had similar internalization capacity were both able cross-present via DC-SIGN. Interestingly, simultaneous triggering TLR4 resulted translocation cytosol, proteasome-dependent processing increased activation. Understanding dynamics DC-SIGN-mediated essential design optimal DC-SIGN-targeting vaccination strategies aimed at enhancing responses.

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