Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens

Cynthia M. Fehres, Hakan Kalay, Sven C.M. Bruijns, Sara A.M. Musaafir, Martino Ambrosini, Louis van Bloois, Sandra J. van Vliet, Gerrit Storm, Juan J. Garcia-Vallejo, Yvette van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review

53 Citations (Scopus)


Dendritic cells (DCs) and Langerhans cells (LC) are professional antigen presenting cells (APCs) that initiate humoral and cellular immune responses. Targeted delivery of antigen towards DC- or LC-specific receptors enhances vaccine efficacy. In this study, we compared the efficiency of glycan-based antigen targeting to both the human DC-specific C-type lectin receptor (CLR) DC-SIGN and the LC-specific CLR langerin. Since DC-SIGN and langerin are able to recognize the difucosylated oligosaccharide Lewis Y (LeY), we prepared neoglycoconjugates bearing this glycan epitope to allow targeting of both lectins. LeY-modified liposomes, with an approximate diameter of 200 nm, were significantly endocytosed by DC-SIGN+ DCs and mediated efficient antigen presentation to CD4+ and CD8+ T cells. Surprisingly, although langerin bound to LeY-modified liposomes, LCs exposed to LeY-modified liposomes could not endocytose liposomes nor mediate antigen presentation to T cells. However, LCs mediated an enhanced cross-presentation when antigen was delivered through langerin using LeY-modified synthetic long peptides. In contrast, LeY-modified synthetic long peptides were recognized by DC-SIGN, but did not trigger antigen internalization nor antigen cross-presentation. These data demonstrate that langerin and DC-SIGN have different size requirements for antigen uptake. Although using glycans remains an interesting option in the design of anti-cancer vaccines targeting multiple CLRs, aspects such as molecule size and conformation need to be taken in consideration.
Original languageEnglish
Pages (from-to)67-76
JournalJournal of controlled release
Publication statusPublished - 2015


  • METIS-315205
  • IR-99647


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