Antigen structure affects cellular routing through DC-SIGN

Significance Dendritic cells (DCs) express cell-surface lectins that bind to carbohydrates displayed on the surface of pathogens. The binding of pathogens to these lectins results in internalization to endosomal compartments, where the pathogens are destroyed and an immune response is initiated. HIV-1 can subvert this process—lectin engagement routes HIV-1 to cellular compartments that allow the virus to evade destruction. We synthesized glycopolymers to test whether the size and physical properties of the antigens impact trafficking. Small polymers trafficked to endosomes, as expected. Alternatively, large particulate polymers localized in the nonendosomal compartments occupied by HIV-1. These data indicate that antigen structure affects routing by DC lectins. Our findings can be exploited to direct cargo to different compartments.