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

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...

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Published in:Cellular & molecular immunology Vol. 14; no. 4; pp. 360 - 370
Main Authors: Fehres, Cynthia M, Duinkerken, Sanne, Bruijns, Sven CM, Kalay, Hakan, van Vliet, Sandra J, Ambrosini, Martino, de Gruijl, Tanja D, Unger, Wendy WJ, Garcia-Vallejo, Juan J, van Kooyk, Yvette
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.04.2017
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ISSN:1672-7681, 2042-0226, 2042-0226
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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 (phC). 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.
AbstractList 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.
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 super(+) 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 super(+) early endosomes. The potency of LCs to enhance CD8 super(+) 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.
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.
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.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.
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.
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 (phC). 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.
Author Cynthia M Fehres Sanne Duinkerken Sven CM Bruijns Hakan Kalay Sandra J van Vliet Martino Ambrosini Tanja D de Gruijl Wendy WJ Unger Juan J Garcia-Vallejo Yvette van Kooyk
AuthorAffiliation Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26456691$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright Chinese Society of Immunology and The University of Science and Technology 2015
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Copyright © 2015 Chinese Society of Immunology and The University of Science and Technology 2015 Chinese Society of Immunology and The University of Science and Technology
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DocumentTitleAlternate Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells
Langerin-mediated antigen cross-presentation
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Issue 4
Keywords early endosomes
langerin
human Langerhans cells
dectin-1
antigen cross-presentation
Language English
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Notes 11-4987/R
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 (phC). 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.
antigen cross-presentation; dectin-1; early endosomes; human Langerhans cells; langerin
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SourceType-Scholarly Journals-1
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OpenAccessLink https://www.nature.com/articles/cmi201587.pdf
PMID 26456691
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PQPubID 2041960
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ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_5380941
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crossref_citationtrail_10_1038_cmi_2015_87
crossref_primary_10_1038_cmi_2015_87
springer_journals_10_1038_cmi_2015_87
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PublicationCentury 2000
PublicationDate 2017-04-01
PublicationDateYYYYMMDD 2017-04-01
PublicationDate_xml – month: 04
  year: 2017
  text: 2017-04-01
  day: 01
PublicationDecade 2010
PublicationPlace London
PublicationPlace_xml – name: London
– name: China
PublicationTitle Cellular & molecular immunology
PublicationTitleAbbrev Cell Mol Immunol
PublicationTitleAlternate Cellular & Molecular Immunology
PublicationYear 2017
Publisher Nature Publishing Group UK
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
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Snippet 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...
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SubjectTerms Antibodies
Antibodies - metabolism
Antigen presentation
Antigen-presenting cells
Antigens
Antigens - metabolism
Antigens, CD - metabolism
Antiviral agents
Biomedical and Life Sciences
Biomedicine
CD8 antigen
Cell Compartmentation
Cell Differentiation - drug effects
Cross-Priming - drug effects
Cross-Priming - immunology
Cytotoxicity
Endocytosis - drug effects
Endosomes
Endosomes - drug effects
Endosomes - metabolism
Humans
Immunology
Immunotherapy
Internalization
Langerhans cells
Langerhans Cells - cytology
Langerhans Cells - drug effects
Langerhans Cells - metabolism
Lectins, C-Type - metabolism
Ligands
Lymphocytes T
Mannose-Binding Lectins - metabolism
Medical Microbiology
Microbiology
Peptides
Peptides - metabolism
Poly I-C - pharmacology
Proteolysis
research-article
Skin
Skin - metabolism
TLR3 protein
Toll-like receptors
Toll-Like Receptors - metabolism
Toll样受体
Tumors
Vaccination
Vaccine
人类
介导
修饰
内化
抗原呈递
早期
细胞亚群
Title Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells
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