Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+early endosomes. The potency of LCs to enhance CD8+T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.

Original languageEnglish
Pages (from-to)360-370
Number of pages11
JournalCellular Immunology
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2017

Cite this

@article{edac95ba6dc84431a9983fc19a1f37aa,
title = "Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells",
abstract = "The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+early endosomes. The potency of LCs to enhance CD8+T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.",
keywords = "Antibodies, Antigens, Antigens, CD, Cell Compartmentation, Cell Differentiation, Cross-Priming, Endocytosis, Endosomes, Humans, Langerhans Cells, Lectins, C-Type, Ligands, Mannose-Binding Lectins, Peptides, Poly I-C, Skin, Toll-Like Receptors, Journal Article",
author = "Fehres, {Cynthia M} and Sanne Duinkerken and Bruijns, {Sven Cm} and Hakan Kalay and {van Vliet}, {Sandra J} and Martino Ambrosini and {de Gruijl}, {Tanja D} and Unger, {Wendy Wj} and Garcia-Vallejo, {Juan J} and {van Kooyk}, Yvette",
year = "2017",
month = "4",
doi = "10.1038/cmi.2015.87",
language = "English",
volume = "14",
pages = "360--370",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

AU - Fehres, Cynthia M

AU - Duinkerken, Sanne

AU - Bruijns, Sven Cm

AU - Kalay, Hakan

AU - van Vliet, Sandra J

AU - Ambrosini, Martino

AU - de Gruijl, Tanja D

AU - Unger, Wendy Wj

AU - Garcia-Vallejo, Juan J

AU - van Kooyk, Yvette

PY - 2017/4

Y1 - 2017/4

N2 - The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+early endosomes. The potency of LCs to enhance CD8+T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.

AB - The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+early endosomes. The potency of LCs to enhance CD8+T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.

KW - Antibodies

KW - Antigens

KW - Antigens, CD

KW - Cell Compartmentation

KW - Cell Differentiation

KW - Cross-Priming

KW - Endocytosis

KW - Endosomes

KW - Humans

KW - Langerhans Cells

KW - Lectins, C-Type

KW - Ligands

KW - Mannose-Binding Lectins

KW - Peptides

KW - Poly I-C

KW - Skin

KW - Toll-Like Receptors

KW - Journal Article

U2 - 10.1038/cmi.2015.87

DO - 10.1038/cmi.2015.87

M3 - Article

VL - 14

SP - 360

EP - 370

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 4

ER -