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

37 Citations (Scopus)

Abstract

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
Volume203
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-315205
  • IR-99647

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