Targeting DC-SIGN via its neck region leads to prolonged antigen residence in early endosomes, delayed lysosomal degradation and cross-presentation

DC_sign1
DC-SIGN is a transmembrane C-type lectin receptor with a long extracellular neck region and a carbohydrate recognition domain (CRD), specifically expressed on antigen-presenting dendritic cells (DCs). Targeting antigens to DC-specific receptors, such as DC-SIGN, induces potent T cell-mediated immune responses. Thus far, only antibodies binding the CRD have been employed to target antigens to DC-SIGN.

In an article recently published in BLOOD, researchers of the Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, in collaboration with colleagues of the TWINCORE Centre for Experimental and Clinical Infection Research in Hannover demonstrated that anti-neck and anti-CRD antibodies were differentially routed within DCs. Whereas anti-CRD antibodies were mainly routed to late endosomes and lysosomes, anti-neck antibodies remained associated with early endosomal compartments positive for EEA1 and MHC class I for several hours following internalization.

Finally, the authors demonstrated that cross-presentation of protein antigen conjugated to anti-neck antibodies was ~1000 fold more effective than non-conjugated antigen.These studies demonstrate that anti-neck antibodies trigger a distinct mode of DC-SIGN internalization that shows potential for targeted anti-tumor vaccination strategies.

Paul J. Tacken, Wiebke Ginter, Luciana Berod, Luis J. Cruz, Ben Joosten, Tim Sparwasser, Carl G. Figdor, Alessandra Cambi

Link to article

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