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

25 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

Fingerprint

Cross-Priming
Dendritic Cells
Polysaccharides
Antigens
Liposomes
Langerhans Cells
Antigen Presentation
C-Type Lectins
Endocytosis
T-Lymphocytes
Peptides
Cancer Vaccines
Antigen-Presenting Cells
Humoral Immunity
Lectins
Cellular Immunity
Epitopes
Vaccines

Keywords

  • METIS-315205
  • IR-99647

Cite this

Fehres, C. M., Kalay, H., Bruijns, S. C. M., Musaafir, S. A. M., Ambrosini, M., van Bloois, L., ... van Kooyk, Y. (2015). Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens. Journal of controlled release, 203, 67-76. https://doi.org/10.1016/j.jconrel.2015.01.040
Fehres, Cynthia M. ; Kalay, Hakan ; Bruijns, Sven C.M. ; Musaafir, Sara A.M. ; Ambrosini, Martino ; van Bloois, Louis ; van Vliet, Sandra J. ; Storm, Gerrit ; Garcia-Vallejo, Juan J. ; van Kooyk, Yvette. / Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens. In: Journal of controlled release. 2015 ; Vol. 203. pp. 67-76.
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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.",
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Fehres, CM, Kalay, H, Bruijns, SCM, Musaafir, SAM, Ambrosini, M, van Bloois, L, van Vliet, SJ, Storm, G, Garcia-Vallejo, JJ & van Kooyk, Y 2015, 'Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens' Journal of controlled release, vol. 203, pp. 67-76. https://doi.org/10.1016/j.jconrel.2015.01.040

Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens. / Fehres, Cynthia M.; Kalay, Hakan; Bruijns, Sven C.M.; Musaafir, Sara A.M.; Ambrosini, Martino; van Bloois, Louis; van Vliet, Sandra J.; Storm, Gerrit; Garcia-Vallejo, Juan J.; van Kooyk, Yvette.

In: Journal of controlled release, Vol. 203, 2015, p. 67-76.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cross-presentation through langerin and DC-SIGN targeting requires different formulation of glycan-modified antigens

AU - Fehres, Cynthia M.

AU - Kalay, Hakan

AU - Bruijns, Sven C.M.

AU - Musaafir, Sara A.M.

AU - Ambrosini, Martino

AU - van Bloois, Louis

AU - van Vliet, Sandra J.

AU - Storm, Gerrit

AU - Garcia-Vallejo, Juan J.

AU - van Kooyk, Yvette

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - METIS-315205

KW - IR-99647

U2 - 10.1016/j.jconrel.2015.01.040

DO - 10.1016/j.jconrel.2015.01.040

M3 - Article

VL - 203

SP - 67

EP - 76

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

ER -